TI: Highly increased CSF concentrations of cholesterol precursors in Smith-Lemli-Opitz syndrome.
AU: van-Rooij-A; Nijenhuis-AA; Wijburg-FA; Schutgens-RB
AD: Academic Medical Center, University of Amsterdam, The Netherlands.
SO: J-Inherit-Metab-Dis. 1997 Aug; 20(4): 578-80
ISSN: 0141-8955
PY: 1997
LA: ENGLISH
CP: NETHERLANDS
AB: The Smith-Lemli-Opitz syndrome is a genetic disorder characterized by typical clinical features including reduced myelination of both brain and peripheral nervous system and defective cholesterol biosynthesis. In patients this results in very low cholesterol concentrations and accumulation of cholesterol precursors in plasma, tissues, cultured cells and faeces. We now show that the cholesterol concentration in CSF of Smith-Lemli-Opitz patients is markedly decreased and that 7- and 8-dehydrocholesterol concentrations are highly increased in comparison to controls. Moreover, dietary treatment of patients with cholesterol seems not to affect CSF cholesterol concentration.
MESH: Cholestadienols-cerebrospinal-fluid; Chromatography,-Gas; Dehydrocholesterols-cerebrospinal-fluid; Infant-; Infant,-Newborn
MESH: *Cholesterol-cerebrospinal-fluid; *Smith-Lemli-Opitz-Syndrome-cerebrospinal-fluid
TG: Female; Human; Male
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE
RN: 0; 0; 434-16-2; 57-88-5; 70741-38-7
NM: Cholestadienols; Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol; cholesta-5,8-dien-3-beta-ol
AN: 97411417
UD: 9712
MEDLINE EXPRESS (R) 10/97-1/98 2 of 60
TI: Smith-Lemli-Opitz syndrome: further delineation of the phenotype.
AU: Worthington-S; Goldblatt-J
AD: Department of Clinical Genetics, Sydney Children's Hospital, NSW, Australia.
SO: Clin-Dysmorphol. 1997 Jul; 6(3): 263-6
ISSN: 0962-8827
PY: 1997
LA: ENGLISH
CP: ENGLAND
MESH: Abnormalities,-Multiple-genetics; Abnormalities,-Multiple-pathology; Adrenal-Glands-metabolism; Cholesterol-metabolism; Cleft-Lip-genetics; Cleft-Lip-pathology; Extremities-abnormalities; Genes,-Recessive; Infant,-Newborn; Phenotype-; Smith-Lemli-Opitz-Syndrome-genetics; Smith-Lemli-Opitz-Syndrome-metabolism
MESH: *Smith-Lemli-Opitz-Syndrome-pathology
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: 57-88-5
NM: Cholesterol
AN: 97363906
UD: 9711
MEDLINE EXPRESS (R) 10/97-1/98 3 of 60
TI: [Smith-Lemli-Opitz syndrome: abnormal cholesterol biosynthesis]
TO: Sindrome de Smith-Lemli-Opitz. Anomalia en la sintesis de colesterol.
AU: de-la-Torre-Verdu-M; Vazquez-Lopez-M; Carrasco-Marina-L; Giros-ML; Quijano-Roy-S; Arregui-Sierra-A
AD: Servicio de Pediatria, Hospital Severo Ochoa, Madrid.
SO: An-Esp-Pediatr. 1997 Jun; 46(6): 617-20
ISSN: 0302-4342
PY: 1997
LA: SPANISH; NON-ENGLISH
CP: SPAIN
MESH: Infant-; Smith-Lemli-Opitz-Syndrome-diagnosis
MESH: *Cholesterol-biosynthesis; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: 57-88-5
NM: Cholesterol
AN: 97378980
UD: 9711
MEDLINE EXPRESS (R) 10/97-1/98 4 of 60
TI: Rapid identification of Smith-Lemli-Opitz syndrome homozygotes and heterozygotes (carriers) by measurement of deficient 7-dehydrocholesterol-delta 7-reductase activity in fibroblasts.
AU: Shefer-S; Salen-G; Honda-A; Batta-A; Hauser-S; Tint-GS; Honda-M; Chen-T; Holick-MF; Nguyen-LB
AD: Department of Medicine, University of Medicine and Dentistry (UMD)-New Jersey Medical School, Newark 07103, USA.
SO: Metabolism. 1997 Jul; 46(7): 844-50
ISSN: 0026-0495
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: To extend the enzyme deficiency in Smith-Lemli-Opitz syndrome (SLOS) to extrahepatic tissues, 7-dehydrocholesterol-delta 7-reductase activity was measured in fibroblasts from 10 controls, five SLOS homozygotes, and five obligate heterozygotes. In cells grown almost to confluence in cholesterol-containing medium (4 mg/dL), the conversion of [1,2-3H]7-dehydrocholesterol to cholesterol (7-dehydrocholesterol-delta 7-reductase activity) was 3.8 times higher in control than in homozygote cells and 2.2 times higher than in heterozygote cells. After 24 hours' exposure of the fibroblasts to cholesterol-deficient medium supplemented with lovastatin, 7-dehydrocholesterol-delta 7-reductase activity increased twofold in controls, but did not change significantly in either heterozygous or homozygous cells. In contrast, the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lathosterol 5-dehydrogenase, two key enzymes that precede 7-dehydrocholesterol-delta 7-reductase in the cholesterol biosynthetic pathway, and low-density lipoprotein (LDL) receptor-mediated binding were equal in control, homozygote, and heterozygote fibroblasts. Further, HMG-CoA reductase activity and LDL receptor-mediated binding increased after exposure of the cells to cholesterol-deficient medium. Fibroblast cholesterol concentrations were approximately equal, although homozygote cells contained 30 times more 7-dehydrocholesterol. Thus, markedly reduced 7-dehydrocholesterol-delta 7-reductase activity that cannot be upregulated after exposure of the cells to cholesterol-deficient medium is diagnostic for the biochemical defect in SLOS. Significantly reduced enzyme activity between the levels in controls and homozygotes without accumulation of 7-dehydrocholesterol in fibroblasts identified heterozygotes.
MESH: Fibroblasts-enzymology; Hydroxymethylglutaryl-CoA-Reductases-metabolism; Skin-pathology; Smith-Lemli-Opitz-Syndrome-pathology
MESH: *Heterozygote-; *Homozygote-; *Oxidoreductases-deficiency; *Skin-enzymology; *Smith-Lemli-Opitz-Syndrome-enzymology; *Smith-Lemli-Opitz-Syndrome-genetics
TG: Human; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK26756DKNIDDK; HL17818HLNHLBI
RN: EC 1.; EC 1.1.1.88; EC 1.3.1.21
NM: Oxidoreductases; Hydroxymethylglutaryl-CoA-Reductases; 7-dehydrocholesterol-reductase
AN: 97369354
UD: 9710
MEDLINE EXPRESS (R) 1/97-9/97 5 of 60
TI: First-trimester diagnosis of Smith-Lemli-Opitz syndrome.
AU: Sharp-P; Haan-E; Fletcher-JM; Khong-TY; Carey-WF
AD: Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia.
SO: Prenat-Diagn. 1997 Apr; 17(4): 355-61
ISSN: 0197-3851
PY: 1997
LA: ENGLISH
CP: ENGLAND
AB: We report here the prenatal diagnosis of Smith-Lemli-Opitz (SLO) syndrome in the first trimester by direct measurement of 7-dehydrocholesterol (7-DHC) in a chorionic villus (CV) biopsy. The proband was diagnosed clinically at birth and the diagnosis was confirmed biochemically by demonstrating elevated 7-DHC in plasma. The family pursued prenatal diagnosis in their fourth, fifth, and sixth pregnancies. The fourth pregnancy spontaneously miscarried at 9 weeks' gestation. Analysis in both direct and cultured curetting tissue (identified as similar to CV tissue) showed an abnormal tissue neutral sterol pattern with an elevated 7-DHC concentration. The fifth pregnancy also miscarried spontaneously at 9 weeks but no tissue of unequivocal fetal origin could be identified to allow biochemical investigation. In the sixth pregnancy, ultrasound examination at the time of CV sampling showed a thickened nuchal fold. Direct analysis of the CV sample revealed elevated levels of 7-DHC consistent with the diagnosis of SLO. The pregnancy was terminated and both fetal tissue and cultured fetal cells showed marked increases in 7-DHC, confirming the prenatal diagnosis.
MESH: Cells,-Cultured; Chorionic-Villi-chemistry; Dehydrocholesterols-analysis; Fetal-Diseases-diagnosis; Infant,-Newborn; Pregnancy-; Pregnancy-Trimester,-First
MESH: *Prenatal-Diagnosis; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Case-Report; Female; Human
PT: JOURNAL-ARTICLE
RN: 0; 434-16-2
NM: Dehydrocholesterols; 7-dehydrocholesterol
AN: 97304103
UD: 9709
MEDLINE EXPRESS (R) 1/97-9/97 6 of 60
TI: MRI in Smith-Lemli-Opitz syndrome type I.
AU: Trasimeni-G; Di-Biasi-C; Iannilli-M; Orlandi-L; Boscherini-B; Balducci-R; Gualdi-GF
AD: CT and MR Unit, Universita di Roma La Sapienza, Italy.
SO: Childs-Nerv-Syst. 1997 Jan; 13(1): 47-9
ISSN: 0256-7040
PY: 1997
LA: ENGLISH
CP: GERMANY
AB: We describe a single case of a polymalformational syndrome in which the MR findings were of great help in the final diagnosis of Smith-Lemli-Opitz syndrome (SLOS) type I. MRI was performed for evaluation of the brain morphology since the clinical and laboratory findings were suggestive but not unequivocally indicative of SLOS. MRI findings of frontal lobe hypoplasia, cortical migration defect, and abnormalities of median line structures prompted the final diagnosis of SLOS.
MESH: Brain-pathology; Cerebral-Cortex-abnormalities; Cerebral-Cortex-pathology; Cerebral-Ventricles-pathology; Corpus-Callosum-abnormalities; Corpus-Callosum-pathology; Diagnosis,-Differential; Frontal-Lobe-abnormalities; Frontal-Lobe-pathology; Infant-; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Brain-abnormalities; *Magnetic-Resonance-Imaging; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 97237224
UD: 9708
MEDLINE EXPRESS (R) 1/97-9/97 7 of 60
TI: Molecular analysis of deletion (17)(p11.2p11.2) in a family segregating a 17p paracentric inversion: implications for carriers of paracentric inversions.
AU: Yang-SP; Bidichandani-SI; Figuera-LE; Juyal-RC; Saxon-PJ; Baldini-A; Patel-PI
AD: G.R.A.C.E. Pediatrics, Davis, CA, USA.
SO: Am-J-Hum-Genet. 1997 May; 60(5): 1184-93
ISSN: 0002-9297
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: A male child with multiple congenital anomalies initially was clinically diagnosed as having Smith-Lemli-Opitz syndrome (SLOS). Subsequent cytogenetic studies revealed an interstitial deletion of 17p11.2, which is associated with Smith-Magenis syndrome (SMS). Biochemical studies were not supportive of a diagnosis of SLOS, and the child did not display the typical SMS phenotype. The father's karyotype showed a paracentric inversion of 17p, with breakpoints in p11.2 and p13.3, and the same inversion was also found in two of the father's sisters. FISH analyses of the deleted and inverted 17p chromosomes indicated that the deletion was similar to that typically seen in SMS patients and was found to bracket the proximal inversion breakpoint. Available family members were genotyped at 33 polymorphic DNA loci in 17p. These studies determined that the deletion was of paternal origin and that the inversion was of grandpaternal origin. Haplotype analysis demonstrated that the 17p11.2 deletion arose following a recombination event involving the father's normal and inverted chromosome 17 homologues. A mechanism is proposed to explain the simultaneous deletion and apparent "reinversion" of the recombinant paternal chromosome. These findings have implications for prenatal counseling of carriers of paracentric inversions, who typically are considered to bear minimal reproductive risk.
MESH: Chromosome-Banding; Genetic-Counseling; Genotype-; Haplotypes-; Heterozygote-; In-Situ-Hybridization,-Fluorescence; Infant,-Newborn; Models,-Genetic; Pedigree-; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Abnormalities,-Multiple-genetics; *Base-Sequence; *Chromosomes,-Human,-Pair-17-genetics; *Inversion-Genetics; *Sequence-Deletion
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD28458HDNICHD
AN: 97294410
UD: 9708
MEDLINE EXPRESS (R) 1/97-9/97 8 of 60
TI: New treatment strategy for Smith-Lemli-Opitz syndrome [letter]
AU: Jira-P; Wevers-R; de-Jong-J; Rubio-Gozalbo-E; Smeitink-J
SO: Lancet. 1997 Apr 26; 349(9060): 1222
ISSN: 0140-6736
PY: 1997
LA: ENGLISH
CP: ENGLAND
MESH: Dehydrocholesterols-blood; Enzyme-Inhibitors-therapeutic-use; Hydroxymethylglutaryl-CoA-Reductases-antagonists-and-inhibitors; Infant-; Lovastatin-therapeutic-use; Smith-Lemli-Opitz-Syndrome-drug-therapy
MESH: *Anticholesteremic-Agents-therapeutic-use; *Exchange-Transfusion,-Whole-Blood; *Lovastatin-analogs-and-derivatives; *Smith-Lemli-Opitz-Syndrome-therapy
TG: Case-Report; Female; Human
PT: LETTER
RN: EC 1.1.1.88; 0; 0; 0; 434-16-2; 75330-75-5; 79902-63-9
NM: Hydroxymethylglutaryl-CoA-Reductases; Anticholesteremic-Agents; Dehydrocholesterols; Enzyme-Inhibitors; 7-dehydrocholesterol; Lovastatin; simvastatin
AN: 97277566
UD: 9707
SB: AIM
MEDLINE EXPRESS (R) 1/97-9/97 9 of 60
TI: Maternal serum marker levels in two pregnancies affected with Smith-Lemli-Opitz syndrome [letter]
AU: Canick-JA; Abuelo-DN; Bradley-LA; Tint-GS
SO: Prenat-Diagn. 1997 Feb; 17(2): 187-9
ISSN: 0197-3851
PY: 1997
LA: ENGLISH
CP: ENGLAND
MESH: Pregnancy-
MESH: *alpha-Fetoproteins-analysis; *Estriol-blood; *Gonadotropins,-Chorionic-blood; *Smith-Lemli-Opitz-Syndrome-blood; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Female; Human
PT: LETTER
RN: 0; 0; 50-27-1
NM: alpha-Fetoproteins; Gonadotropins,-Chorionic; Estriol
AN: 97215418
UD: 9707
MEDLINE EXPRESS (R) 1/97-9/97 10 of 60
TI: Linkage analysis in a family with the Opitz GBBB syndrome refines the location of the gene in Xp22 to a 4 cM region.
AU: May-M; Huston-S; Wilroy-RS; Schwartz-C
AD: Center for Molecular Studies, J.C. Self Research Institute, Greenwood Genetic Center, S.C. 29646, USA.
SO: Am-J-Med-Genet. 1997 Jan 20; 68(2): 244-8
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: The Opitz GBBB syndrome (OS) is characterized in part by widely spaced inner ocular canthi and hypospadias. Recently, linkage analysis showed that the gene for the X-linked form to be located in an 18 cM region spanning Xp22. We have now conducted linkage analysis in a family previously published as having the BBB syndrome and found tight linkage to DXS7104 (Z = 3.3, theta = 0.0). Our data narrows the candidate region to 4 cM and should facilitate the identification and characterization of one of the genes involved in midline development.
MESH: DNA-analysis; Haplotypes-; Microsatellite-Repeats; Pedigree-
MESH: *Linkage-Genetics; *Smith-Lemli-Opitz-Syndrome-genetics; *X-Chromosome-genetics
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 9007-49-2
NM: DNA
AN: 97180294
UD: 9707
MEDLINE EXPRESS (R) 1/97-9/97 11 of 60
TI: The Smith-Lemli-Opitz syndrome: a potentially fatal birth defect caused by a block in the last enzymatic step in cholesterol biosynthesis.
AU: Tint-GS; Batta-AK; Xu-G; Shefer-S; Honda-A; Irons-M; Elias-ER; Salen-G
AD: Research Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey 07019, USA.
SO: Subcell-Biochem. 1997; 28: 117-44
ISSN: 0306-0225
PY: 1997
LA: ENGLISH
CP: ENGLAND
MESH: Cholestadienols-metabolism; Dehydrocholesterols-metabolism; Disease-Models,-Animal; Enzyme-Inhibitors-pharmacology; Liver-enzymology; Oxidoreductases-antagonists-and-inhibitors; Oxidoreductases-deficiency; Oxidoreductases-metabolism; Piperazines-pharmacology; Smith-Lemli-Opitz-Syndrome-genetics; Smith-Lemli-Opitz-Syndrome-therapy
MESH: *Cholesterol-biosynthesis; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Animal; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-ACADEMIC
CN: HD31932HDNICHD; DK18707DKNIDDK; HL17818HLNHLBI
RN: EC 1.; EC 1.3.1.21; 0; 0; 0; 0; 434-16-2; 57-88-5; 70741-38-7; 86621-92-3
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Cholestadienols; Dehydrocholesterols; Enzyme-Inhibitors; Piperazines; 7-dehydrocholesterol; Cholesterol; cholesta-5,8-dien-3-beta-ol; BM-15766
AN: 97245625
UD: 9707
MEDLINE EXPRESS (R) 1/97-9/97 12 of 60
TI: [Smith Lemli-Opitz syndrome]
AU: Ieshima-A
AD: Department of Pediatrics, Tottori Prefectural Kaike Rehabilitation Center for Disabled Children.
SO: Ryoikibetsu-Shokogun-Shirizu. 1996(15): 302-4
PY: 1996
LA: JAPANESE; NON-ENGLISH
CP: JAPAN
MESH: *Smith-Lemli-Opitz-Syndrome
TG: Female; Human; Male
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 97200088
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 13 of 60
TI: Pathogenesis of malformations in a rodent model for Smith-Lemli-Opitz syndrome.
AU: Dehart-DB; Lanoue-L; Tint-GS; Sulik-KK
AD: Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599-7090, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 328-37
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: The fact that Smith-Lemli-Opitz syndrome (SLOS), a syndrome comprising major malformations involving a number of organ systems, results from an abnormality in cholesterol biosynthesis, was discovered only recently. Utilizing a drug (BM 15.766) to inhibit the same step in cholesterol biosynthesis as is abnormal in those affected with SLOS, we have developed a rat model that presents with abnormalities observed as early as gestational day 12 that appear to be consistent with some of those subsequent malformations that comprise the human syndrome. Abnormalities of the brain and face include deficiency in the midline region of the upper face, narrowing of the forebrain hemispheres and of the cerebral aqueduct, and deficiency in the developing lower jaw. Associated pathogenesis, as observed on gestational day 11 in histological sections and with scanning electron microscopy, involves abnormal cell populations at the rim of the developing forebrain and in the alar plate of the lower midbrain and hind-brain. The affected cells appear abnormally rounded up, having apparently lost their normal cell contacts. The potential basis for the selective vulnerability of this cell population and the impact of its vulnerability relative to subsequent dysmorphogenesis is discussed.
MESH: Cholesterol-blood; Disease-Models,-Animal; Embryo-ultrastructure; Pregnancy-; Rats-; Rats,-Wistar; Smith-Lemli-Opitz-Syndrome-chemically-induced
MESH: *Piperazines-toxicity; *Smith-Lemli-Opitz-Syndrome-pathology; *Teratogens-toxicity
TG: Animal; Female; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AA08204AANIAAA; HD28845HDNICHD; HD31932HDNICHD
RN: 0; 0; 57-88-5; 86621-92-3
NM: Piperazines; Teratogens; Cholesterol; BM-15766
AN: 97177029
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 14 of 60
TI: Smith-Lemli-Opitz syndrome produced in rats with AY 9944 treated by intravenous injection of lipoprotein cholesterol.
AU: Chambers-CM; McLean-MP; Ness-GC
AD: Department of Biochemistry, College of Medicine, University of South Florida, Tampa 33612, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 322-7
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: A limitation to treating Smith-Lemli-Opitz infants by giving dietary cholesterol is their impaired ability to absorb cholesterol due to a deficiency of bile acids. Since intravenously administered lipoprotein cholesterol should not require bile acids for uptake into tissues, we tested the effects of this form of cholesterol on tissue cholesterol and 7-dehydrocholesterol levels in an animal model of SLO, created by feeding rats 0.02% AY 9944. Intravenous administration of 15 mg of bovine cholesterol supertrate twice daily increased serum cholesterol levels from 11 to over 250 mg/dl. This treatment increased liver cholesterol levels from 309 to over 900 micrograms/g and lowered hepatic 7-dehydrocholesterol levels from 1546 to 909 micrograms/g. A combination of iv cholesterol and 2% dietary cholesterol was most effective as it raised hepatic cholesterol levels to 1950 micrograms/g, which is 50% above normal. 7-Dehydrocholesterol levels were decreased to 760 micrograms/g. Similar responses were seen for heart, lung, kidney, and testes. Brain sterol levels were not significantly affected. AY 9944 caused a modest increase in hepatic HMG-CoA reductase activity. Administration of dietary cholesterol together with iv cholesterol lowered hepatic HMG-CoA reductase activity to barely detectable levels. The data indicate that the combination of iv and dietary cholesterol was most effective in raising cholesterol levels, lowering 7-dehydrocholesterol levels, and inhibiting de novo cholesterol biosynthesis.
MESH: Anticholesteremic-Agents; AY-9944; Cholesterol-metabolism; Cholesterol,-Dietary-therapeutic-use; Combined-Modality-Therapy; Dehydrocholesterols-metabolism; Disease-Models,-Animal; Enzyme-Inhibitors; Injections,-Intravenous; Oxidoreductases-antagonists-and-inhibitors; Rats-; Rats,-Sprague-Dawley; Smith-Lemli-Opitz-Syndrome-chemically-induced; Smith-Lemli-Opitz-Syndrome-diet-therapy
MESH: *Cholesterol-therapeutic-use; *Lipoproteins-therapeutic-use; *Smith-Lemli-Opitz-Syndrome-drug-therapy
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 0; 0; 0; 0; 0; 0; 366-93-8; 434-16-2; 57-88-5
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; lipoprotein-cholesterol; Anticholesteremic-Agents; Cholesterol,-Dietary; Dehydrocholesterols; Enzyme-Inhibitors; Lipoproteins; AY-9944; 7-dehydrocholesterol; Cholesterol
AN: 97177028
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 15 of 60
TI: Cholesterol and bile acid replacement therapy in children and adults with Smith-Lemli-Opitz (SLO/RSH) syndrome.
AU: Nwokoro-NA; Mulvihill-JJ
AD: Department of Oral and Maxillofacial Surgery, University of Pittsburgh, Pennsylvania 15261-1931, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 315-21
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Tint et al. [N Engl J Med 1994, 330:107-113], working with blood samples from the Smith-Lemli-Opitz syndrome (SLOS) patients of Irons and Elias showed the biochemical basis of this disorder to be a cholesterol biosynthesis defect [Irons et al., Lancet, 1993, 341:1414]. Based on this finding, clinical protocols for cholesterol and bile acid replacement therapy were established in a few centers including the University of Pittsburgh. We report our experience with bile acid and/or cholesterol replacement therapy in six patients with SLOS, now aged 3-27 years, with a confirmed biochemical diagnosis. Levels of plasma cholesterol and 7-dehydrocholesterol were correlated with periodic clinical evaluations over 8-27 months of therapy. There was a marked improvement in the growth of all the children. There was also an increase in the plasma cholesterol level in all the children and an overall increase in their percent sterol as cholesterol. Subjective improvement was also noted in their development. Although there was no significant change in the plasma cholesterol level of the older patients, there was a marked improvement in their behavior and in their quality of life.
MESH: Adolescence-; Adult-; Child-; Child,-Preschool; Drug-Therapy,-Combination
MESH: *Bile-Acids-and-Salts-therapeutic-use; *Cholesterol-therapeutic-use; *Smith-Lemli-Opitz-Syndrome-drug-therapy
TG: Case-Report; Human
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE
RN: 0; 57-88-5
NM: Bile-Acids-and-Salts; Cholesterol
AN: 97177027
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 16 of 60
TI: Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial.
AU: Irons-M; Elias-ER; Abuelo-D; Bull-MJ; Greene-CL; Johnson-VP; Keppen-L; Schanen-C; Tint-GS; Salen-G
AD: Department of Pediatrics, Boston Floating Hospital, Tufts-New England Medical Center, Massachusetts, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 311-4
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Patients with the RSH or Smith-Lemli-Optiz syndrome (SLOS) have an inborn error of cholesterol biosynthesis which results in a deficiency of cholesterol and an elevation of the cholesterol precursor, 7-dehydrocholesterol. A treatment protocol consisting of administration of cholesterol +/- bile acids was initiated in an attempt to correct the biochemical abnormalities seen. Fourteen patients (8 female, 6 male: ages 2 months to 15 years) have now been treated for 6-15 months. Three patients received cholesterol alone, while 11 patients received cholesterol and one or more bile acids. Biochemical improvement in sterol levels and in the ratio of cholesterol to total sterols was noted in all patients. The most marked improvement was noted in patients presenting with initial cholesterol levels < 40 mg/dl. No toxicity was observed. Clinical improvement in growth and neurodevelopmental status was also observed.
MESH: Adolescence-; Bile-Acids-and-Salts-adverse-effects; Child-; Child,-Preschool; Cholesterol-adverse-effects; Cholesterol-blood; Clinical-Protocols; Drug-Therapy,-Combination; Infant-; Smith-Lemli-Opitz-Syndrome-blood; Sterols-blood
MESH: *Bile-Acids-and-Salts-therapeutic-use; *Cholesterol-therapeutic-use; *Smith-Lemli-Opitz-Syndrome-drug-therapy
TG: Female; Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY
CN: RR00054RRNCRR
RN: 0; 0; 57-88-5
NM: Bile-Acids-and-Salts; Sterols; Cholesterol
AN: 97177026
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 17 of 60
TI: Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS).
AU: Elias-ER; Irons-MB; Hurley-AD; Tint-GS; Salen-G
AD: Department of Pediatrics, Tufts-New England Medical Center, Boston, Massachusetts, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 305-10
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: We describe the clinical effects of cholesterol supplementation in 6 children with the RSH-"Smith-Lemli-Opitz" syndrome (SLOS). The children ranged in age from birth to 11 years at the onset of therapy, with pretreatment cholesterol levels ranging from 8 to 62 mg/dl. Clinical benefits of therapy were seen in all patients, irrespective of age at onset of treatment, or severity of cholesterol defect. Effects of treatment included improved growth, more rapid developmental progress, and a lessening of problem behaviors. Pubertal progression in older patients, a better tolerance of infection, improvement of gastrointestinal symptoms, and a diminution in photosensitivity and skin rashes were also noted. There were no adverse reactions to treatment with cholesterol. This preliminary study suggests that cholesterol supplementation may be of benefit to patients with the SLOS.
MESH: Behavior-; Bile-Acids-and-Salts-administration-and-dosage; Bile-Acids-and-Salts-therapeutic-use; Cataract-drug-therapy; Cataract-physiopathology; Child-; Child,-Preschool; Cholesterol,-Dietary-administration-and-dosage; Cholesterol,-Dietary-therapeutic-use; Endocrine-Glands-physiology; Follow-Up-Studies; Gastrointestinal-Diseases-drug-therapy; Gastrointestinal-Diseases-physiopathology; Growth-; Infant-; Infant,-Newborn; Infection-drug-therapy; Infection-physiopathology; Skin-Diseases-drug-therapy; Skin-Diseases-physiopathology; Smith-Lemli-Opitz-Syndrome-diet-therapy; Smith-Lemli-Opitz-Syndrome-physiopathology
MESH: *Cholesterol-therapeutic-use; *Smith-Lemli-Opitz-Syndrome-drug-therapy
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE
RN: 0; 0; 57-88-5
NM: Bile-Acids-and-Salts; Cholesterol,-Dietary; Cholesterol
AN: 97177025
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 18 of 60
TI: Direct analysis of filter paper blood specimens for identification of Smith-Lemli-Opitz syndrome using time-of-flight secondary ion mass spectrometry.
AU: Zimmerman-PA; Hercules-DM; Naylor-EW
AD: Department of Chemistry, University of Pittsburgh, Pennsylvania, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 300-4
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: In this study, time-of-flight secondary ion mass spectrometry was used to distinguish between blood of normal infants and that of individuals with Smith-Lemli-Opitz (SLO) syndrome. SLO syndrome results in an abnormally low concentration of blood cholesterol and an elevated concentration of 7-dehydrocholesterol. Blood was spotted on filter paper and analyzed directly with no extractions or separations. Results showed that using ratios of fragment ions for cholesterol/dehydrocholesterol, patients with SLO and normal individuals could be unambiguously distinguished. Unknown samples from 28 individuals were obtained and identified correctly.
MESH: Adult-; Child-; Child,-Preschool; Cholesterol-blood; Dehydrocholesterols-blood; Evaluation-Studies; Filtration-; Infant-; Infant,-Newborn; Mass-Screening; Smith-Lemli-Opitz-Syndrome-blood
MESH: *Smith-Lemli-Opitz-Syndrome-diagnosis; *Spectrometry,-Mass,-Secondary-Ion
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: MCJ9049
RN: 0; 57-88-5
NM: Dehydrocholesterols; Cholesterol
AN: 97177024
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 19 of 60
TI: Increased expression of low-density lipoprotein receptors in a Smith-Lemli-Opitz infant with elevated bilirubin levels.
AU: Ness-GC; Lopez-D; Borrego-O; Gilbert-Barness-E
AD: Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33612, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 294-9
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: We report on an infant girl with severe RSH or Smith-Lemli-Opitz syndrome with hyperbilirubinemia. The infant died at age 2 months. Sterol analysis of liver and brain tissues showed marked elevations of 7-dehydrocholesterol with decreased levels of cholesterol. Immunocytochemical analysis demonstrated remarkable increases in low-density lipoprotein (LDL) receptors in these tissues, indicative of a deficiency in available cholesterol for tissue needs.
MESH: Brain-metabolism; Brain-pathology; Dehydrocholesterols-metabolism; Infant-; Liver-metabolism; Liver-pathology; Pancreas-pathology; Smith-Lemli-Opitz-Syndrome-pathology
MESH: *Bilirubin-metabolism; *Receptors,-LDL-metabolism; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Case-Report; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 434-16-2; 635-65-4
NM: Dehydrocholesterols; Receptors,-LDL; 7-dehydrocholesterol; Bilirubin
AN: 97177023
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 20 of 60
TI: Screening for abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome: rapid determination of plasma 7-dehydrocholesterol by ultraviolet spectrometry.
AU: Honda-A; Batta-AK; Salen-G; Tint-GS; Chen-TS; Shefer-S
AD: Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 288-93
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: The Smith-Lemli-Opitz syndrome (SLOS) is a common condition caused by deficiency of 7-dehydrocholesterol delta 7-reductase. The syndrome can usually be diagnosed by demonstrating markedly increased plasma concentrations of the cholesterol precursor, 7-dehydrocholesterol. We describe a simple and rapid method for detection of plasma 7-dehydrocholesterol by use of ultraviolet (UV) spectrometry. Lipids were extracted from plasma by addition of ethanol and n-hexane, and the n-hexane phase was directly subjected to spectrometry. The absorption maxima characteristics of 7-dehydrocholesterol (lambda max 271, 282, and 294 nm) were observed in patients' plasma but not in controls. For quantitative measurements, absorbance at 282 nm was used. Since this absorbance is the sum of the absorbance derived from 7-dehydrocholesterol and background absorbance, the concentrations of 7-dehydrocholesterol in various plasma samples were quantified by subtracting estimated background absorbance at 282 nm from observed absorbance at 282 nm. The results correlated well with total (free plus esterified) 7-dehydrocholesterol concentrations measured by gas-liquid chromatographic method. The UV spectrometric assay was sensitive enough to detect increased 7-dehydrocholesterol in cultured skin fibroblasts from patients grown in delipidated medium. The present method will make it possible to screen plasma or fibroblasts to detect the syndrome rapidly in general clinical laboratories.
MESH: Cells,-Cultured; Chromatography,-Gas; Fibroblasts-metabolism; Spectrophotometry,-Ultraviolet
MESH: *Cholesterol-biosynthesis; *Dehydrocholesterols-blood; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Comparative-Study; Female; Human; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL17818HLNHLBI; HD31932HDNICHD
RN: 0; 434-16-2; 57-88-5
NM: Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 97177022
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 21 of 60
TI: Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts: diagnosis of a biochemically atypical case of the syndrome.
AU: Honda-A; Tint-GS; Salen-G; Kelley-RI; Honda-M; Batta-AK; Chen-TS; Shefer-S
AD: Department of Medicine, Veterans Affairs Medical Center, East Orange, New Jersey 07018-1095, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 282-7
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: The Smith-Lemli-Opitz syndrome is a common birth defect syndrome caused by a deficiency of 7-dehydrocholesterol delta 7-reductase, an essential enzyme in the biosynthesis of cholesterol. The syndrome can usually be diagnosed easily from the plasma markers of markedly elevated 7-dehydrocholesterol and reduced cholesterol concentrations. However, atypical cases with normal plasma levels of cholesterol with only moderately elevated 7-dehydrocholesterol have been reported. To establish a sensitive method for the biochemical diagnosis of the atypical cases of the syndrome, we measured sterol concentrations of cultured skin fibroblasts. 7-Dehydrocholesterol concentrations in patients' fibroblasts grown in the presence of 10% fetal bovine serum were significantly higher than those in controls and parents (P < 0.0005), but they were not elevated proportionately as much as in plasma. To re-produce the accumulation of 7-dehydrocholesterol, the cells were exposed to delipidated medium to induce sterol biosynthesis. After 4 weeks, 7-dehydrocholesterol concentrations in patients' fibroblasts increased from 2.8 +/- 0.3% to 34 +/- 3% of total sterols (cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol). The increase was also observed in fibroblasts from an atypical patient who has a normal plasma cholesterol level and a 7-dehydrocholesterol concentration of only 0.15 mg/dl. In contrast, cells from parents and controls accumulated very little 7-dehydrocholesterol (< 1% of total sterols). These results demonstrate that cultured fibroblasts exhibit abnormally high accumulation of 7-dehydrocholesterol after cells are exposed to delipidated medium not only in typical patients, but also in an atypical case. The present method is a sensitive procedure for the biochemical diagnosis of this syndrome.
MESH: Adolescence-; Adult-; Child-; Child,-Preschool; Dehydrocholesterols-metabolism; Infant-; Infant,-Newborn; Smith-Lemli-Opitz-Syndrome-metabolism
MESH: *Fibroblasts-metabolism; *Smith-Lemli-Opitz-Syndrome-diagnosis; *Sterols-metabolism
TG: Female; Human; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL17818HLNHLBI; HD31932HDNICHD
RN: 0; 0; 434-16-2
NM: Dehydrocholesterols; Sterols; 7-dehydrocholesterol
AN: 97177021
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 22 of 60
TI: Physical mapping of the chromosome 7 breakpoint region in an SLOS patient with t(7;20) (q32.1;q13.2).
AU: Alley-TL; Scherer-SW; Huizenga-JJ; Tsui-LC; Wallace-MR
AD: Department of pediatrics (Division of Genetics), University of Florida College of Medicine, Gainesville, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 279-81
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by multiple congenital anomalies and mental retardation. SLOS has an associated defect in cholesterol biosynthesis, but the molecular genetic basis of this condition has not yet been elucidated. Previously our group reported a patient with a de novo balanced translocation [t(7;20)(q32.1;q13.2)] fitting the clinical and biochemical profile of SLOS. Employing fluorescence in situ hybridization (FISH), a 1.8 Mb chromosome 7-specific yeast artificial chromosome (YAC) was identified which spanned the translocation breakpoint in the reported patient. The following is an update of the on-going pursuit to physically and genetically map the region further, as well as the establishment of candidate genes in the 7q32.1 breakpoint region.
MESH: Cloning,-Molecular; In-Situ-Hybridization,-Fluorescence; Restriction-Mapping
MESH: *Chromosome-Mapping; *Chromosomes,-Human,-Pair-20; *Chromosomes,-Human,-Pair-7; *Smith-Lemli-Opitz-Syndrome-genetics; *Translocation-Genetics
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
AN: 97177020
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 23 of 60
TI: Cardiovascular malformations in Smith-Lemli-Opitz syndrome.
AU: Lin-AE; Ardinger-HH; Ardinger-RH Jr; Cunniff-C; Kelley-RI
AD: Department of Pediatrics University of Kansas, Kansas City, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 270-8
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: We reviewed 215 patients (59 new, 156 from the literature) with Smith-Lemli-Opitz syndrome (SLOS), and found that 95 (44%) had a cardiovascular malformation (CVM). Classifying CVMs by disordered embryonic mechanisms, there were 5 (5.3%) class 1 (ectomesenchymal tissue migration abnormalities), 56 (58.9%) class II (abnormal intracardiac blood flow), 25 (26.3%) class IV (abnormal extracellular matrix), and 5 (5.3%) class V (abnormal targeted growth). Comparing the frequencies of individual CVMs in this series with a control group (the Baltimore-Washington Infant Study), there were 6 individual CVMs which showed a significant difference from expected values. When frequencies of CVMs in SLOS were analyzed by mechanistic class, classes IV and V were significantly more frequent, and class I significantly less frequent, than the control group. Although CVMs in SLOS display mechanistic heterogeneity, with an overall predominance of class II CVMs, the developmental error appears to favor alteration of the cardiovascular developmental mechanisms underlying atrioventricular canal and anomalous pulmonary venous return. This information should assist the clinical geneticist evaluating a patient with possible SLOS, and should suggest research direction for the mechanisms responsible for the SLOS phenotype.
MESH: Phenotype-
MESH: *Heart-Defects,-Congenital-pathology; *Smith-Lemli-Opitz-Syndrome-pathology
TG: Female; Human; Male
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-MULTICASE
AN: 97177019
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 24 of 60
TI: Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism.
AU: Cunniff-C; Kratz-LE; Moser-A; Natowicz-MR; Kelley-RI
AD: Department of Pediatrics, University of Arizona, Steele Memorial Children's Research Center, Tucson, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 263-9
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: RSH/Smith-Lemli-Opitz (RSH/SLO) syndrome is an autosomal recessive malformation syndrome recently shown to be associated with a severe deficiency of cholesterol biosynthesis and markedly elevated plasma and tissue levels of 7-dehydrocholesterol (7-DHC), the immediate precursor of cholesterol in the Kandutsch-Russell biosynthetic pathway. Because these biochemical abnormalities permit a reassessment of RSH/SLO on biochemical criteria rather than less specific physical criteria, we review here the clinical and biochemical characteristics of our first 80 patients with abnormally increased levels of 7-DHC. The study population included 68 index patients and 12 additional relatives identified by quantification of 7-DHC and cholesterol in plasma, amniotic fluid, or cultured fibroblasts, lymphoblasts, or amniocytes. As demonstrated in other clinical syndromes when redefined biochemically, we have found a wider range of clinical expression of RSH/SLO than previously recognized. These newly recognized atypical RSH/SLO patients included several with no malformations other than syndactyly of the toes and, at the other extreme, patients with frank holoprosencephaly or multiple visceral anomalies who died in utero. Syndactyly of toes 2 and 3 was the most common malformation, occurring in all but one of 80 patients. The best biochemical predictor of clinical severity was the plasma cholesterol level, which decreased with increasing clinical severity. However, at least 10% of patients, including one newborn infant, had normal cholesterol levels at the time of diagnosis and would have been missed without specific quantification of 7-DHC. Not unexpectedly, several patients carrying a clinical diagnosis of RSH/SLO were found to have normal levels of all plasma sterols and apparently normal cholesterol biosynthesis in cultured cells. A comparison of the frequency of anomalies in our biochemically identified patients with similar data from previously reported clinical series suggests that up to 25% of reports of RSH/SLO in the literature may describe genetic conditions other than RSH/SLO with 7-DHC-emia.
MESH: Adolescence-; Adult-; Child-; Child,-Preschool; Infant-; Smith-Lemli-Opitz-Syndrome-pathology
MESH: *Cholesterol-metabolism; *Dehydrocholesterols-metabolism; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Female; Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 434-16-2; 57-88-5
NM: Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 97177018
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 25 of 60
TI: Smith-Lemli-Opitz syndrome: thirty-year follow-up of "S" of "RSH" syndrome.
AU: Pauli-RM; Williams-MS; Josephson-KD; Tint-GS
AD: Department of Medical Genetics, University of Wisconsin-Madison 53705, USA.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 260-2
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: We have reassessed patient "S," one of the first 3 individuals recognized to have Smith-Lemli-Opitz (or RSH) syndrome, at age 34 years, and we describe his physical, developmental, and behavioral manifestations. This reassessment provides formal evidence that this individual has the cholesterol biosynthetic defect which is thought to be the cause of Smith-Lemli-Opitz syndrome. Dietary manipulation appears to have had a beneficial effect on the patient's behavior and suggests that even in adults with this condition, dietary cholesterol supplementation may be indicated.
MESH: Adult-; Cholesterol,-Dietary-therapeutic-use; Follow-Up-Studies; Smith-Lemli-Opitz-Syndrome-diet-therapy
MESH: *Smith-Lemli-Opitz-Syndrome-physiopathology
TG: Case-Report; Human; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD31932HDNICHD; DK18707DKNIDDK; HL17818HLNHLBI
RN: 0
NM: Cholesterol,-Dietary
AN: 97177017
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 26 of 60
TI: Smith-Lemli-Opitz syndrome diagnosed in a 130-year-old anatomical specimen.
AU: Oostra-RJ; Baljet-B; Schutgens-RB; Hennekam-RC
AD: Department of Clinical Genetics, Free University Hospital, Amsterdam, The Netherlands.
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 257-9
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: The Museum Vrolik collection of human anatomy comprises 360 recently re-described specimens with congenital anomalies. The external findings in one of these specimens, originally described by Willem Vrolik (1801-1863) 130 years ago, were suggestive of Smith-Lemli-Opitz (SLO) syndrome. Cholesterol synthesis was analyzed in skin biopsies, obtained from the suspected SLO specimen and a control specimen. The cholesterol levels in the SLO specimen and in the control specimen were in the proportion of 1 to 45. This confirms the diagnosis in this specimen which, to our knowledge, represents the oldest known case of SLO syndrome.
MESH: Cadaver-; History-of-Medicine,-19th-Cent.; Infant,-Newborn; Netherlands-; Smith-Lemli-Opitz-Syndrome-pathology
MESH: *Smith-Lemli-Opitz-Syndrome-history
TG: Human; Male
PT: HISTORICAL-ARTICLE; JOURNAL-ARTICLE
AN: 97177016
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 27 of 60
TI: A new face for an old syndrome [editorial]
AU: Kelley-RI
SO: Am-J-Med-Genet. 1997 Jan 31; 68(3): 251-6
ISSN: 0148-7299
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
MESH: Cholesterol-deficiency; Cholesterol-metabolism; Smith-Lemli-Opitz-Syndrome-diagnosis; Smith-Lemli-Opitz-Syndrome-epidemiology; Smith-Lemli-Opitz-Syndrome-metabolism; Smith-Lemli-Opitz-Syndrome-therapy; Sterols-chemistry
MESH: *Smith-Lemli-Opitz-Syndrome
TG: Human
PT: EDITORIAL; MEETING-REPORT
RN: 0; 57-88-5
NM: Sterols; Cholesterol
AN: 97177015
UD: 9706
MEDLINE EXPRESS (R) 1/97-9/97 28 of 60
TI: Measurement of 3 beta-hydroxysteroid delta 7-reductase activity in cultured skin fibroblasts utilizing ergosterol as a substrate: a new method for the diagnosis of the Smith-Lemli-Opitz syndrome.
AU: Honda-M; Tint-GS; Honda-A; Batta-AK; Chen-TS; Shefer-S; Salen-G
AD: Department of Medicine, Veterans Affairs Medical Center, East Orange, NJ 07018, USA.
SO: J-Lipid-Res. 1996 Nov; 37(11): 2433-8
ISSN: 0022-2275
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: A new sensitive and specific method for the evaluation of 3 beta-hydroxysteroid delta 7-reductase activity, the defective enzyme in the Smith-Lemli-Opitz (SLO) syndrome, is described. The assay is based on the use of gas chromatography-mass spectrometry with selected-ion monitoring to measure the mass of brassicasterol (ergosta-5,22-dien-3 beta-ol) produced by the incubation of ergosterol (ergosta-5,7,22-trien-3 beta-ol) with cultured human skin fibroblasts. Although the conversion of ergosterol to brassicasterol was slower than the transformation of [3H]7-dehydrocholesterol to [3H] cholesterol, cells from control subjects produced brassicasterol efficiently. In contrast, cells form SLO patients produced very little brassicasterol (P < 0.0001, patients vs. parents or vs. controls). These results indicate that the reduction of ergosterol can be used as an assay for 3 beta-hydroxysteroid delta 7-reductase in human skin fibroblasts, which avoids the many problems caused by the instability and lack of availability of radiolabeled 7-dehydrocholesterol. The present method made it possible to diagnose the SLO syndrome with high sensitivity and reliability using a commercially available compound.
MESH: Cholestadienols-analysis; Fibroblasts-enzymology; Mass-Fragmentography; Stigmasterol-analysis
MESH: *Ergosterol-metabolism; *Oxidoreductases-analysis; *Skin-enzymology; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Human; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK18707DKNIDDK; HL17818HLNHLBI; HD31932HDNICHD
RN: EC 1.; EC 1.3.1.21; 0; 474-67-9; 57-87-4; 83-48-7
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Cholestadienols; brassicasterol; Ergosterol; Stigmasterol
AN: 97133135
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 29 of 60
TI: Cholesta-5,7,9(11)-trien-3 beta-ol found in plasma of patients with Smith-Lemli-Opitz syndrome indicates formation of sterol hydroperoxide.
AU: De-Fabiani-E; Caruso-D; Cavaleri-M; Galli-Kienle-M; Galli-G
AD: Institute of Pharmacological Sciences, University of Milan, Italy.
SO: J-Lipid-Res. 1996 Nov; 37(11): 2280-7
ISSN: 0022-2275
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by accumulation of cholesta-5,7-dien-3 beta-0l caused by a deficiency of the enzyme desaturating this sterol to cholesterol. In addition to other unusual sterols recently found in plasma of patients with SLOS, namely cholesta-5,8-dien-3 beta-ol and 19-nor-cholesta-5,7,9 (10)-trien-3 beta-ol we have detected a trienol and we describe here its identification as cholesta-5,7,9 (11)-trien-3 beta-ol by GC-MS and by comparison with a synthetic standard. We tested the possibility that the trienol may be formed by radical oxidation of cholesta-5,7-dien-3 beta-ol accumulated in plasma of patients with SLOS because it is known to be formed by decomposition of 7-hydroperoxy-cholesta-5,8-dien-3 beta-ol, which is a product of cholesta-5,7-dien-3 beta-ol photooxidation. Incubation of cholesta-5,7-dien-3 beta-ol with rat liver microsomes in the presence of ADP/Fe2+ and NADPH gave rise to a number of oxygenated sterols. Among these, analysis by particle-beam LC-MS under CI conditions indicated the presence of 7-hydroperoxy-cholesta-5,8-dien-3 beta-ol and of cholesta-5,7,9(11)-trien-3 beta-ol which is known to derive from the oxidation of the 7-hydroperoxide. From these results we conclude that cholesta-5,7-dien-3 beta-ol accumulated in tissues of patients with SLOS may be oxidized by oxygen radicals giving rise to oxygenated sterols. Some of these compounds may be toxic and may contribute to worsen the pathological picture in patients with SLOS.
MESH: Dehydrocholesterols-metabolism; Mass-Fragmentography; Microsomes,-Liver-metabolism; Nuclear-Magnetic-Resonance; NADP-metabolism; Rats-; Rats,-Sprague-Dawley
MESH: *Cholestenes-blood; *Smith-Lemli-Opitz-Syndrome-blood
TG: Animal; Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 0; 434-16-2; 51982-45-7; 53-59-8
NM: Cholestenes; Dehydrocholesterols; 7-dehydrocholesterol; cholesta-5,7,9-trien-3-beta-ol; NADP
AN: 97133120
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 30 of 60
TI: Phenotypic diversity in the Smith-Lemli-Opitz syndrome.
AU: Seller-MJ; Flinter-FA; Docherty-Z; Fagg-N; Newbould-M
AD: South East Thames Regional Genetics Centre, London, UK. m.seller@umds.ac.uk
SO: Clin-Dysmorphol. 1997 Jan; 6(1): 69-73
ISSN: 0962-8827
PY: 1997
LA: ENGLISH
CP: ENGLAND
AB: The phenotype of four cases of Smith-Lemli-Opitz syndrome (SLO) with proven defects in cholesterol biosynthesis are compared, and shown to be markedly disparate even between sibs, and demonstrate the dilemma for the clinician. The advent of a biochemical test for SLO has been enormously valuable in determining which patients are truly affected by the condition, but because of the wide phenotypic variation, a diagnosis on clinical features alone remains problematic.
MESH: Infant,-Newborn
MESH: *Abnormalities,-Multiple-genetics; *Phenotype-; *Smith-Lemli-Opitz-Syndrome-genetics
TG: Case-Report; Female; Human
PT: JOURNAL-ARTICLE
AN: 97171166
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 31 of 60
TI: Inhibition of 7-dehydrocholesterol reductase by the teratogen AY9944: a rat model for Smith-Lemli-Opitz syndrome.
AU: Kolf-Clauw-M; Chevy-F; Wolf-C; Siliart-B; Citadelle-D; Roux-C
AD: Toxicology Department, Ecole Nationale Veterinaire d'Alfort, Maisons-Alfort, France.
SO: Teratology. 1996 Sep; 54(3): 115-25
ISSN: 0040-3709
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Our aim is to verify the validity of a rat model proposed for Smith-Lemli-Opitz (SLO) syndrome, a developmental disorder characterized by a defect in 7-dehydrocholesterol-delta 7 (7DHC)-reductase and by facial dysmorphism close to the holoprosencephaly caused by the teratogen AY9944. We investigated the sterol profile in rats treated with AY9944 blocking 7DHC-reductase. AY9944 was given orally to rats on gestation day 3 (D3). The sera were sampled for kinetic data on D3, D6, D9, D12, and D21. Cholesterol was measured in parallel by the routine enzymatic method and by the gas chromatography/mass spectrometry (GC-MS) procedure used in SLO diagnosis. In addition to sterols, we dosed steroid hormones punctually on D4 and on D10, and examined D21 fetuses in other animals. The enzymatic method was not specific for cholesterol, and measured 70% pure 7DHC added to a normal serum. On D21, 77% live fetuses showed pituitary agenesis. Cholesterol was rapidly reduced by more than 50% on D6 involving an accumulation of 7DHC, 8DHC, and trienols, as identified in SLO-affected children. The most abundant 7DHC reached a maximum from D9 to D12, equaling cholesterol on D9 (11 mg/dl). On D10, the magnitudes of hypocholesterolemic and of 7DHC accumulation were found to be dose-dependent. Progesterone was reduced as early as 24 hr after treatment and dropped to 40% of the levels in the controls on D10, correlating to the decrease in cholesterolemia. This rat model reproduces the same biochemical perturbations as seen in SLO, strongly suggesting that aberrant sterols (7DHC, 8DHC, or nortrienol) may contribute to the developmental defects.
MESH: Cholesterol-metabolism; Disease-Models,-Animal; Estradiol-metabolism; Oxidoreductases-metabolism; Progesterone-metabolism; Rats-; Rats,-Wistar; Smith-Lemli-Opitz-Syndrome-enzymology
MESH: *AY-9944-pharmacology; *Oxidoreductases-antagonists-and-inhibitors; *Smith-Lemli-Opitz-Syndrome-metabolism; *Teratogens-pharmacology
TG: Animal
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 0; 366-93-8; 50-28-2; 57-83-0; 57-88-5
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Teratogens; AY-9944; Estradiol; Progesterone; Cholesterol
AN: 97140706
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 32 of 60
TI: Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: does abnormal cholesterol metabolism affect the function of Sonic Hedgehog?
AU: Kelley-RL; Roessler-E; Hennekam-RC; Feldman-GL; Kosaki-K; Jones-MC; Palumbos-JC; Muenke-M
AD: Kennedy Krieger Institute, Johns Hopkins University, Baltimore, Maryland, USA.
SO: Am-J-Med-Genet. 1996 Dec 30; 66(4): 478-84
ISSN: 0148-7299
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is an autosomal recessive malformation syndrome associated with increased levels of 7-dehydro-cholesterol (7-DHC) and a defect of cholesterol biosynthesis at the level of 3 beta-hydroxy-steroid-delta7-reductase (7-DHC reductase). Because rats exposed to inhibitors of 7-DHC reductase during development have a high frequency of holoprosencephaly (HPE) [Roux et al., 1979], we have undertaken a search for biochemical evidence of RSH/SLOS and other possible defects of sterol metabolism among patients with various forms of HPE. We describe 4 patients, one with semilobar HPE and three others with less complete forms of the HPE sequence, in whom we have made a biochemical diagnosis of RSH/SLOS. The clinical and biochemical spectrum of these and other patients with RSH/SLOS suggests a role of abnormal sterol metabolism in the pathogenesis of their malformations. The association of HPE and RSH/SLOS is discussed in light of the recent discoveries that mutations in the embryonic patterning gene, Sonic Hedgehog (SHH), can cause HPE in humans and that the sonic hedgehog protein product undergoes autoproteolysis to form a cholesterol-modified active product. These clinical, biochemical, and molecular studies suggest that HPE and other malformations in SLOS may be caused by incomplete or abnormal modification of the sonic hedgehog protein and, possible, other patterning proteins of the hedgehog class, a hypothesis testable in somatic cell systems.
MESH: Cells,-Cultured; Child,-Preschool; Dehydrocholesterols-metabolism; Fetal-Death; Holoprosencephaly-complications; Holoprosencephaly-genetics; Infant,-Newborn; Smith-Lemli-Opitz-Syndrome-genetics; Smith-Lemli-Opitz-Syndrome-pathology
MESH: *Cholesterol-metabolism; *Holoprosencephaly-metabolism; *Proteins-physiology; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Female; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 5T32HD07107HDNICHD; DK44933DKNIDDK; HD28732HDNICHD
RN: 0; 0; 0; 434-16-2; 57-88-5
NM: hedgehog-protein,-vertebrate; Dehydrocholesterols; Proteins; 7-dehydrocholesterol; Cholesterol
AN: 97143462
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 33 of 60
TI: Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome.
AU: Biesecker-LG; Kang-S; Schaffer-AA; Abbott-M; Kelley-RI; Allen-JC; Clericuzio-C; Grebe-T; Olney-A; Graham-JM Jr
AD: National Institutes of Health, National Center for Human Genome Research, Bethesda, MD 20892-4470, USA.
SO: J-Med-Genet. 1996 Nov; 33(11): 947-51
ISSN: 0022-2593
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than-2.0. We conclude that hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus.
MESH: Chromosome-Mapping; Hamartoma-genetics; Linkage-Genetics; Pedigree-; Polydactyly-; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Cholesterol-biosynthesis; *Chromosomes,-Human,-Pair-7; *Hamartoma-metabolism; *Hypothalamic-Diseases-genetics; *Hypothalamic-Diseases-metabolism
TG: Female; Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK44933DKNIDDK; HD24061HDNICHD
RN: 57-88-5
NM: Cholesterol
AN: 97107976
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 34 of 60
TI: Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome.
AU: Salen-G; Tint-GS; Xu-G; Batta-AK; Irons-M; Elias-ER
AD: Veterans Affairs Medical Center, East Orange, NJ, USA.
SO: Ital-J-Gastroenterol. 1995 Dec; 27(9): 506-8
ISSN: 0392-0623
PY: 1995
LA: ENGLISH
CP: ITALY
AB: We measured plasma sterol concentrations in 7 homozygotes with the Smith-Lemli-Opitz syndrome, 5 heterozygotes and rats treated with BM 15.766, the competitive inhibitor of 7-dehydrocholesterol 7-reductase. Low cholesterol associated with markedly elevated 7-dehydrocholesterol concentrations were detected in the plasma of all homozygotes and inhibitor-treated rats. Heterozygotes were clinically normal and, like control subjects, showed only trace amounts of 7-dehydrocholesterol in plasma. We conclude that the Smith-Lemli-Opitz syndrome is due to an inherited defect in 7 dehydrocholesterol 7-reductase which causes the accumulation of 7-dehydrocholesterol and a deficiency of cholesterol in the plasma, a biochemical abnormality that can be reproduced in rats treated with BM 15.766.
MESH: Adolescence-; Adult-; Anticholesteremic-Agents-pharmacology; Child-; Child,-Preschool; Cholesterol-blood; Dehydrocholesterols-blood; Enzyme-Inhibitors-pharmacology; Heterozygote-; Homozygote-; Infant-; Middle-Age; Oxidoreductases-antagonists-and-inhibitors; Oxidoreductases-deficiency; Piperazines-pharmacology; Rats-; Rats,-Sprague-Dawley; Smith-Lemli-Opitz-Syndrome-enzymology; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Cholesterol-biosynthesis; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Animal; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL17818HLNHLBI; DK18707DKNIDDK
RN: EC 1.; EC 1.3.1.21; 0; 0; 0; 0; 434-16-2; 57-88-5; 86621-92-3
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Anticholesteremic-Agents; Dehydrocholesterols; Enzyme-Inhibitors; Piperazines; 7-dehydrocholesterol; Cholesterol; BM-15766
AN: 97078397
UD: 9705
MEDLINE EXPRESS (R) 1/97-9/97 35 of 60
TI: Abnormal cholesterol biosynthesis in sitosterolaemia and the Smith-Lemli-Opitz syndrome.
AU: Salen-G; Shefer-S; Batta-AK; Tint-GS; Xu-G; Honda-A
AD: VA Medical Center, East Orange, NJ 07018, USA.
SO: J-Inherit-Metab-Dis. 1996; 19(4): 391-400
ISSN: 0141-8955
PY: 1996
LA: ENGLISH
CP: NETHERLANDS
AB: We investigated the enzyme defects in two inherited disorders of cholesterol biosynthesis: sitosterolaemia and the Smith-Lemli-Opitz syndrome. In sitosterolaemic homozygotes, plasma plant sterols (sitosterol and campesterol) concentrations are elevated because of enhanced intestinal absorption and diminished removal. Underlying these changes is very low cholesterol biosynthesis to provide extra sterol for cell growth. Extremely reduced activities of HMG-CoA reductase, the rate-controlling enzyme for cholesterol biosynthesis, caused by deficient HMG-CoA reductase mRNA is responsible and is the suspected inherited abnormality. The Smith-Lemli-Opitz syndrome is caused by a block in the last reaction in the cholesterol biosynthetic pathway, the conversion of 7-dehydrocholesterol to cholesterol, which is catalysed by 7-dehydrocholesterol delta 7-reductase. As a result, low plasma and tissue cholesterol with high 7-dehydrocholesterol levels are found in homozygotes, who show characteristic phenotypes of mental retardation, facial dysmorphism, and organ and limb congenital anomalies. Similar biochemical findings are produced in rats fed BM 15,766, an inhibitor of 7-dehydrocholesterol delta 7-reductase. Interestingly, feeding cholesterol can suppress abnormal cholesterol biosynthesis and improve symptoms in homozygotes and rats fed BM 15,766.
MESH: Oxidoreductases-deficiency; Oxidoreductases-genetics; Oxidoreductases-metabolism; Rats-; Smith-Lemli-Opitz-Syndrome-metabolism
MESH: *Cholesterol-biosynthesis; *Sitosterols-blood; *Smith-Lemli-Opitz-Syndrome-enzymology
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 1.; EC 1.3.1.21; 0; 57-88-5
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Sitosterols; Cholesterol
AN: 97038982
UD: 9704
MEDLINE EXPRESS (R) 1/97-9/97 36 of 60
TI: Pitfalls in measuring plasma cholesterol in the Smith-Lemli-Opitz syndrome.
AU: Jira-PE; de-Jong-JG; Janssen-Zijlstra-FS; Wendel-U; Wevers-RA
AD: Institute of Pediatrics, University Hospital Nijmegen, The Netherlands.
SO: Clin-Chem. 1997 Jan; 43(1): 129-33
ISSN: 0009-9147
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Correct quantitative results for plasma cholesterol, 7-dehydrocholesterol (7-DHC), and 8-dehydrocholesterol (8-DHC) are invaluable for making the correct diagnosis in patients with the Smith-Lemli-Opitz syndrome (SLO) and for biochemical monitoring of these patients during therapy. The enzymatic method for cholesterol measurement based on cholesterol oxidase gives falsely high values for plasma cholesterol in samples from patients with SLO. Both 7-DHC and 8-DHC contribute substantially to the test result, given that they are accepted substrates of cholesterol oxidase. All cholesterol methods making use of this enzyme are expected to give unreliable results with plasma samples from SLO patients. Cholesterol values found with these methods may be low-normal in individual cases with SLO. Therefore, other techniques for measuring cholesterol, 7-DHC, and 8-DHC, e.g., gas chromatography, should be used for diagnosing these patients and for follow-up during therapy. However, a normal value for plasma cholesterol, as obtained by gas chromatography, does not exclude SLO. The diagnosis should always be confirmed or excluded by testing for the presence of high concentrations of 7-DHC and 8-DHC in plasma. We found that one patient with a severe form of the disease had a plasma cholesterol concentration of 20 micromol/L-to our knowledge, the lowest value ever recorded in a human being.
MESH: Adult-; Child-; Cholestadienols-blood; Cholesterol-Oxidase; Chromatography,-Gas; Dehydrocholesterols-blood; False-Positive-Reactions; Infant-; Infant,-Newborn; Reference-Values; Smith-Lemli-Opitz-Syndrome-diagnosis
MESH: *Cholesterol-blood; *Smith-Lemli-Opitz-Syndrome-blood
TG: Human
PT: JOURNAL-ARTICLE
RN: EC 1.1.3.6; 0; 0; 434-16-2; 57-88-5; 70741-38-7
NM: Cholesterol-Oxidase; Cholestadienols; Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol; cholesta-5,8-dien-3-beta-ol
AN: 97144467
UD: 9704
MEDLINE EXPRESS (R) 1/97-9/97 37 of 60
TI: Sex reversal in an infant with Smith-Lemli-Opitz syndrome, type II: evidence for 5-alpha reductase deficiency.
AU: Salbert-BA; Schwartz-ID; Grunt-JA
AD: Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
SO: J-Pediatr-Endocrinol-Metab. 1996 Jan-Feb; 9(1): 67-9
PY: 1996
LA: ENGLISH
CP: ENGLAND
MESH: Infant,-Newborn; Sex-Differentiation-Disorders-enzymology
MESH: *Sex-Differentiation-Disorders-etiology; *Smith-Lemli-Opitz-Syndrome-enzymology; *Testosterone-5-alpha-Reductase-deficiency
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 1.3.99.5
NM: Testosterone-5-alpha-Reductase
AN: 97041865
UD: 9704
MEDLINE EXPRESS (R) 1/97-9/97 38 of 60
TI: Effect of YM 9429, a potent teratogen, on cholesterol biosynthesis in cultured cells and rat liver microsomes.
AU: Honda-A; Tint-GS; Shefer-S; Batta-AK; Honda-M; Salen-G
AD: Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, USA.
SO: Steroids. 1996 Sep; 61(9): 544-8
ISSN: 0039-128X
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: YM 9429 (cis-1-[4-(p-menthan-8-yloxy)phenyl]piperidine) is a hypolipidemic agent with a potent and specific teratogenicity, inducing cleft palate and skeletal variations in rats. Since cleft palate is generally observed in the Smith-Lemli-Opitz syndrome, a common syndrome of multiple congenital anomalies caused by reduced activity of 7-dehydrocholesterol delta 7-reductase (3 beta-hydroxysteroid delta 7-reductase), the final enzyme in the cholesterol biosynthetic pathway, YM 9429 was suspected of being an inhibitor of this enzyme. To prove this hypothesis, YM 9429 was added to cultured human skin fibroblasts and to cultured Morris hepatoma cells and incubated with [5-3H]mevalonolactone. After 24 h, radiolabeled 7-dehydrocholesterol accumulated in the cells, whereas the formation of radiolabeled cholesterol was markedly reduced. The results indicate that YM 9429 inhibits the conversion of 7-dehydrocholesterol to cholesterol catalyzed by the microsomal enzyme 7-dehydrocholesterol delta 7-reductase. In rat liver microsomes, the mode of inhibition was found to be noncompetitive, with a Ki of 40 microM. These results suggest that YM 9429 induced developmental abnormalities in rats by the same mechanism as the Smith-Lemli-Opitz syndrome. This compound might be useful for studying the pathogenesis of anomalies in animal models of the Smith-Lemli-Opitz syndrome.
MESH: Cholesterol-metabolism; Fibroblasts-drug-effects; Fibroblasts-metabolism; Hydroxymethylglutaryl-CoA-Reductases-drug-effects; Hydroxymethylglutaryl-CoA-Reductases-metabolism; Kinetics-; Liver-Neoplasms,-Experimental-drug-therapy; Liver-Neoplasms,-Experimental-metabolism; Liver-Neoplasms,-Experimental-pathology; Mevalonic-Acid-analogs-and-derivatives; Mevalonic-Acid-metabolism; Microsomes,-Liver-enzymology; Oxidoreductases-antagonists-and-inhibitors; Oxidoreductases-drug-effects; Oxidoreductases-metabolism; Piperazines-pharmacology; Rats-; Smith-Lemli-Opitz-Syndrome-enzymology; Tumor-Cells,-Cultured
MESH: *Cholesterol-biosynthesis; *Enzyme-Inhibitors-pharmacology; *Microsomes,-Liver-drug-effects; *Piperidines-pharmacology; *Teratogens-pharmacology
TG: Animal; Human; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK18707DKNIDDK; HL17818HLNHLBI; HD31932HDNICHD
RN: EC 1.; EC 1.1.1.88; EC 1.3.1.21; EC 1.3.3.2; 0; 0; 0; 0; 150-97-0; 503-48-0; 57-88-5; 72056-79-2; 80-99-9; 86621-92-3
NM: Oxidoreductases; Hydroxymethylglutaryl-CoA-Reductases; 7-dehydrocholesterol-reductase; lathosterol-delta-5-dehydrogenase; Enzyme-Inhibitors; Piperazines; Piperidines; Teratogens; Mevalonic-Acid; mevalonolactone; Cholesterol; YM-9429; lathosterol; BM-15766
AN: 97037574
UD: 9703
MEDLINE EXPRESS (R) 1/97-9/97 39 of 60
TI: Changes in serum sterols of rats treated with 7-dehydrocholesterol-delta 7-reductase inhibitors: comparison to levels in humans with Smith-Lemli-Opitz syndrome.
AU: Wolf-C; Chevy-F; Pham-J; Kolf-Clauw-M; Citadelle-D; Mulliez-N; Roux-C
AD: Laboratoire de Biochimie, CHU Saint Antoine, Paris.
SO: J-Lipid-Res. 1996 Jun; 37(6): 1325-33
ISSN: 0022-2275
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The impaired conversion of 7-dehydrocholesterol to cholesterol, as a result of a permanent inhibition of the activity of 7-dehydrocholesterol-delta 7-reductase, has been reported in the Smith-Lemli-Opitz (SLO) syndrome (1, 2). For the purpose of experimental teratology, an animal disease model consisting of the offspring of pregnant rats treated with AY 9944 or BM 15766, inhibitors of 7-dehydrocholesterol-delta 7-reductase, was established. The present study compares the profiles of sterols in rat serum, obtained after transient treatment with inhibitors, with profiles of sterols obtained from patients with the permanent enzyme defect. AY 9944 (single dose of 50, 75, or 100 mg/kg) or BM 15766 (60, 75, or 90 mg/kg per day for 11 days) induces hypocholesterolemia and accumulation of 7-dehydrocholesterol and aberrant sterols in rat serum. The aberrant sterols in the treated rats are similar to those detected in human SLO patients by gas chromatography coupled to mass spectrometry (1, 3, 4) and were identified as 7- and 8-dehydrocholesterol, two trienols (I and II), and 19-nor-5,7,9(10)-cholestatrien-3 beta-ol. The time- and dose-dependences of the biochemical alterations are compared to the teratogenic abnormalities induced by inhibitors. The dietary cholesterol supplementation that suppresses embryo malformations induced by AY 9944 prevents severe hypocholesterolemia and decreases the aberrant sterol levels. As a function of time after intoxication, the 8-dehydrocholesterol to 7-dehydrocholesterol ratio increases, suggested that 8-dehydrocholesterol is derived from the gradual conversion of the accumulated 7-dehydrocholesterol. The ratio of 8-dehydrocholesterol to 7-dehydrocholesterol is higher in human SLO than in the animal disease model. This may be explained by a permanent block in 7-dehydrocholesterol-delta 7-reductase in SLO compared to a transient inhibition of this enzyme in the animal model.
MESH: Child-; Cholestadienols-blood; Cholesterol-blood; Dehydrocholesterols-blood; Disease-Models,-Animal; Heterozygote-; Pregnancy-; Rats-; Rats,-Wistar; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *AY-9944-pharmacology; *Enzyme-Inhibitors-pharmacology; *Oxidoreductases-antagonists-and-inhibitors; *Piperazines-pharmacology; *Prenatal-Exposure-Delayed-Effects; *Smith-Lemli-Opitz-Syndrome-blood; *Sterols-blood
TG: Animal; Comparative-Study; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 0; 0; 0; 0; 0; 366-93-8; 434-16-2; 57-88-5; 70741-38-7; 86621-92-3
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Cholestadienols; Dehydrocholesterols; Enzyme-Inhibitors; Piperazines; Sterols; AY-9944; 7-dehydrocholesterol; Cholesterol; cholesta-5,8-dien-3-beta-ol; BM-15766
AN: 96404585
UD: 9703
MEDLINE EXPRESS (R) 1/97-9/97 40 of 60
TI: Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome.
AU: Salen-G; Shefer-S; Batta-AK; Tint-GS; Xu-G; Honda-A; Irons-M; Elias-ER
AD: VA Medical Center, East Orange, NJ 07019, USA.
SO: J-Lipid-Res. 1996 Jun; 37(6): 1169-80
ISSN: 0022-2275
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The Smith-Lemli-Opitz syndrome is caused by an inherited defect in 7-dehydrocholesterol-delta7-reductase, the enzyme that catalyzes the last reaction in cholesterol biosynthesis, the conversion of 7-dehydrocholesterol to cholesterol. As a result, deficient cholesterol is produced and the precursor 7-dehydrocholesterol and derivatives (8-dehydrocholesterol and 19-nor-5,7,9(10)-cholestatrien-3 beta-ol) accumulate. Tissues (especially brain) deprived of cholesterol, or because of the deposited sterol precursors and derivatives, develop abnormally and function poorly. Replacement with dietary cholesterol may help correct the biochemical defects and improve symptoms.
MESH: Adolescence-; Adult-; Child-; Child,-Preschool; Dehydrocholesterols-metabolism; Fetal-Death; Heterozygote-; Incidence-; Infant-; Infant,-Newborn; Oxidoreductases-deficiency; Smith-Lemli-Opitz-Syndrome-epidemiology; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Cholesterol-metabolism; *Oxidoreductases-genetics; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Female; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: HL18717HLNHLBI; DK26756DKNIDDK
RN: EC 1.; EC 1.3.1.21; 0; 434-16-2; 57-88-5
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 96404569
UD: 9703
MEDLINE EXPRESS (R) 1/97-9/97 41 of 60
TI: [Identification of impaired cholesterol biosynthesis in a Japanese patient of Smith-Lemli-Opitz syndrome]
AU: Hasui-M; Saito-C; Kasama-T; Taki-T; Yachie-A
AD: Department of Pediatrics, National Sanatorium Io Hospital, Ishikawa.
SO: No-To-Hattatsu. 1997 Jan; 29(1): 61-6
ISSN: 0029-0831
PY: 1997
LA: JAPANESE; NON-ENGLISH
CP: JAPAN
AB: We reported the decreased level of cholesterol as well as the elevated levels of 7- and 8-dehydrocholesterol in the serum and erythrocytes of a Japanese patient with Smith-Lemli-Opitz syndrome. These findings suggested that the detection of these precursors of cholesterol synthesis should become an important biochemical parameter for this syndrome in which clinical features are not always obvious.
MESH: Adult-; English-Abstract
MESH: *Cholesterol-biosynthesis; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: 57-88-5
NM: Cholesterol
AN: 97139397
UD: 9703
MEDLINE EXPRESS (R) 1/97-9/97 42 of 60
TI: Opitz syndrome in a Japanese male.
AU: Nishiyama-T; Gunji-T; Terunuma-M; Matsui-T
AD: Department of Urology, Koseiren Nagaoka Chuo General Hospital, Japan.
SO: Int-J-Urol. 1996 Jul; 3(4): 326-8
ISSN: 0919-8172
PY: 1996
LA: ENGLISH
CP: JAPAN
AB: There have been only a few reports on Opitz syndrome in Japan. We report here a case of a Japanese male with canthal hypertelorism, bilateral cleft lip and palate, scrotal hypospadias with scrotal transposition, and cryptorchidism, findings that met the criteria for this syndrome. After repair of the cleft lip and palate, urethroplasty was performed at age 2, and bilateral orchiopexy was performed at age 3. At age 5, the child is of normal weight for his age, voids urine smoothly on standing, and has slight mental retardation.
MESH: Child,-Preschool; Japan-ethnology; Smith-Lemli-Opitz-Syndrome-surgery
MESH: *Smith-Lemli-Opitz-Syndrome-ethnology; *Smith-Lemli-Opitz-Syndrome-pathology
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 97001304
UD: 9703
MEDLINE EXPRESS (R) 1/97-9/97 43 of 60
TI: Chromosome 22q11.2 deletion in a boy with Opitz (G/BBB) syndrome.
AU: Fryburg-JS; Lin-KY; Golden-WL
AD: Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
SO: Am-J-Med-Genet. 1996 Mar 29; 62(3): 274-5
ISSN: 0148-7299
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: This report is on a 14-month-old boy with manifestations of Opitz (G/BBB) syndrome in whom a 22q11.2 deletion was found. Deletion analysis was requested because of some findings in this patient reminiscent of velocardiofacial (VCF) syndrome. The extent of aspiration and of respiratory symptoms in this child is not usually seen in VCF syndrome. Opitz syndrome maps to at least two loci, one on Xp, the other on 22q11.2.
MESH: Adult-; Infant-; Smith-Lemli-Opitz-Syndrome-physiopathology
MESH: *Chromosome-Deletion; *Chromosomes,-Human,-Pair-22; *Smith-Lemli-Opitz-Syndrome-genetics
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 97037139
UD: 9702
MEDLINE EXPRESS (R) 1/97-9/97 44 of 60
TI: Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz and the lethal acrodysgenital syndromes.
AU: Cormier-Daire-V; Wolf-C; Munnich-A; Le-Merrer-M; Nivelon-A; Bonneau-D; Journel-H; Fellmann-F; Chevy-F; Roux-C
AD: Service de Genetique, Hopital des Enfants-Malades, Paris, France.
SO: Eur-J-Pediatr. 1996 Aug; 155(8): 656-9
ISSN: 0340-6199
PY: 1996
LA: ENGLISH
CP: GERMANY
AB: The Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterized by dysmorphic facial features with abnormal limbs and genitalia. Two forms have been recognized based on clinical course and severity: the classical SLO (type I) and the lethal acrodysgenital syndrome (type II). Type I SLO has been recently ascribed to a defect in cholesterol synthesis. Taking advantage of a series of seven patients including five type I and two type II SLO, we describe micrognathia, severe microcephaly, major ante and post natal growth retardation and feeding difficulties as consistent features in the disease. In addition, we give support to the presence of abnormal cholesterol levels in the lethal acrodysgenital syndrome but find no correlation between plasma sterol levels and the clinical severity of the disease. CONCLUSION: The identification of the same biochemical defect in both types of Smith-Lemli-Opitz Syndrome suggests that despite major discrepancies in clinical course and severity, type I and type II SLo are probably allelic disorders.
MESH: Child-; Child,-Preschool; Cholesterol-blood; Infant-; Infant,-Newborn; Karyotyping-; Outcome-Assessment-Health-Care; Severity-of-Illness-Index; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Cholesterol-biosynthesis; *Smith-Lemli-Opitz-Syndrome-classification; *Smith-Lemli-Opitz-Syndrome-physiopathology
TG: Female; Human; Male
PT: JOURNAL-ARTICLE
RN: 57-88-5
NM: Cholesterol
AN: 96436903
UD: 9702
MEDLINE EXPRESS (R) 1/97-9/97 45 of 60
TI: Abnormal cholesterol metabolism in Smith-Lemli-Opitz syndrome.
AU: Elias-ER; Irons-M
AD: Boston Floating Hospital for Children at Tufts-New England Medical Center, Massachusetts 02111, USA.
SO: Curr-Opin-Pediatr. 1995 Dec; 7(6): 710-4
ISSN: 1040-8703
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Smith-Lemli-Opitz syndrome (SLOS) is a common autosomal recessive disorder. Children with SLOS present with specific facial dysmorphism and have multiple congenital anomalies including cleft palate, congenital heart disease, genitourinary anomalies, and limb abnormalities. They also manifest severe failure to thrive and mental retardation. A metabolic defect at the final step in the cholesterol biosynthetic pathway has been described in SLOS patients. This defect results in markedly reduced cholesterol levels and abnormal accumulation of cholesterol precursors, particularly 7-dehydrocholesterol. This newly described metabolic defect in humans is one of only a few metabolic errors known to cause multiple birth defects. The biochemical profile of reduced plasma cholesterol levels in association with markedly elevated levels of the cholesterol precursor 7-dehydrocholesterol is now used to confirm the diagnosis of SLOS, which was formerly made on purely clinical grounds. This biochemical abnormality has been confirmed in dozens of patients with SLOS in both the United States and Europe. The severe cholesterol deficiency seen in these patients has multiple effects on health and early childhood development, because cholesterol is an essential component of many cell functions, which explains many of the clinical findings seen in SLOS.
MESH: Child-; Cholesterol-biosynthesis; Cholesterol-blood; Smith-Lemli-Opitz-Syndrome-therapy
MESH: *Cholesterol-deficiency; *Metabolism,-Inborn-Errors-metabolism; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 57-88-5
NM: Cholesterol
AN: 96372201
UD: 9702
MEDLINE EXPRESS (R) 1/97-9/97 46 of 60
TI: Clinical and biochemical screening for Smith-Lemli-Opitz syndrome. Italian SLOS Collaborative Group.
AU: Guzzetta-V; De-Fabiani-E; Galli-G; Colombo-C; Corso-G; Lecora-M; Parenti-G; Strisciuglio-P; Andria-G
AD: Dipartimento di Pediatria, Federico II University, Naples, Italy.
SO: Acta-Paediatr. 1996 Aug; 85(8): 937-42
ISSN: 0803-5253
PY: 1996
LA: ENGLISH
CP: NORWAY
AB: Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomalies/mental retardation disorder possibly due to a defect of delta 7-sterol reductase, leading to low plasma cholesterol levels and to the accumulation of 7-dehydrocholesterol (7-DHC) and other cholesterol precursors. This study aimed to identify clinical features that could potentially be specific indicators for the clinical diagnosis of SLOS, and to test the reliability of ultraviolet spectrophotometry (UVS) as a biochemical screening procedure for the syndrome. Twenty patients with clinical suspicion of SLOS, referred to 11 Italian paediatric and clinical genetic centres, were collected during 1994. In 10 patients the diagnosis was confirmed biochemically by gas chromatography/mass spectrometry (GC/MS) analysis of serum sterols, whereas in the other 10 patients the serum sterol profiles were normal. A comparison between confirmed SLOS patients and biochemically negative subjects did not show clinical signs specific for the syndrome. UVS measurement of 7-DHC correlated well with GC/MS profiles, showing 100% sensitivity and specificity. Four out of five patients had serum bile acid concentrations below the normal range of controls.
MESH: Adolescence-; Bile-Acids-and-Salts-blood; Biological-Markers-blood; Child-; Child,-Preschool; Infant-; Sensitivity-and-Specificity; Spectrophotometry,-Ultraviolet
MESH: *Dehydrocholesterols-blood; *Smith-Lemli-Opitz-Syndrome-blood; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Female; Human; Male
PT: JOURNAL-ARTICLE; MULTICENTER-STUDY
RN: 0; 0; 0; 434-16-2
NM: Bile-Acids-and-Salts; Biological-Markers; Dehydrocholesterols; 7-dehydrocholesterol
AN: 97017274
UD: 9702
MEDLINE EXPRESS (R) 1/97-9/97 47 of 60
TI: Confirmation of defective cholesterol biosynthesis in 2 previously described adult sibs with Smith-Lemli-Opitz syndrome [letter]
AU: De-Die-Smulders-C; Van-de-Meer-S; Spaapen-L; Fryns-JP
SO: Genet-Couns. 1996; 7(2): 161-2
ISSN: 1015-8146
PY: 1996
LA: ENGLISH
CP: SWITZERLAND
MESH: Adult-
MESH: *Cholesterol-biosynthesis; *Smith-Lemli-Opitz-Syndrome-genetics
TG: Case-Report; Human
PT: LETTER
RN: 57-88-5
NM: Cholesterol
AN: 96427836
UD: 9702
MEDLINE EXPRESS (R) 1992-1996 48 of 60
TI: Smith-Lemli-Opitz syndrome: treatment with cholesterol and bile acids [letter]
AU: Ullrich-K; Koch-HG; Meschede-D; Flotmann-U; Seedorf-U
SO: Neuropediatrics. 1996 Apr; 27(2): 111-2
ISSN: 0174-304X
PY: 1996
LA: ENGLISH
CP: GERMANY
MESH: Cholesterol-blood; Dehydrocholesterols-blood; Infant-; Smith-Lemli-Opitz-Syndrome-blood
MESH: *Bile-Acids-and-Salts-administration-and-dosage; *Cholesterol,-Dietary-administration-and-dosage; *Smith-Lemli-Opitz-Syndrome-therapy
TG: Female; Human; Male
PT: LETTER
RN: 0; 0; 0; 434-16-2; 57-88-5
NM: Bile-Acids-and-Salts; Cholesterol,-Dietary; Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 96354312
UD: 9701
MEDLINE EXPRESS (R) 1992-1996 49 of 60
TI: First trimester prenatal diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency).
AU: Mills-K; Mandel-H; Montemagno-R; Soothill-P; Gershoni-Baruch-R; Clayton-PT
AD: Biochemistry Unit, Institute of Child Health, London, United Kingdom.
SO: Pediatr-Res. 1996 May; 39(5): 816-9
ISSN: 0031-3998
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: In Smith-Lemli-Opitz syndrome (SLOs), 7-dehydrocholesterol (7-DHC) accumulated because there is a block in the pathway for synthesis of cholesterol via 7-DHC. Prenatal diagnosis of SLOs has been achieved by analysis of 7-DHC in amniotic fluid obtained at 16-18 wk from pregnancies at risk. The purpose of this study was to investigate 7-DHC and cholesterol concentrations in chorionic villus (CV) samples with a view to performing first trimester prenatal diagnosis. Using a sensitive gas chromatography-mass spectrometry assay it was possible to detect 7-DHC in CV samples obtained as early as 7 wk of gestation. The ration of 7-DHC to cholesterol in placental tissue was shown to be relatively constant over the gestational period of 7-18 wk. We therefore proceeded to analyze the 7-DHC/cholesterol ration in CV samples taken at 10-12 wk of gestation from three pregnancies at risk for SLOs. The results were as follows: patient A, 1.10 x 10(-3); patient B, 1.80 x 10(-3); patient C, 0.091; control range for CVS (8-12 wk), 3.10 x 10(-4) to 1.62 x 10(-3) (mean +/- 2SD; n = 5). The fetus of patient C was diagnosed as affected by SLOs, and the parents requested termination. Analysis of cultured skin fibroblasts confirmed the diagnosis. Pregnancies A and B were diagnosed unaffected, and this was confirmed first by amniocentesis and then by the birth of normal infants at term. We conclude that synthesis of cholesterol via 7-DHC is occurring in the placenta and/or fetus at 10 wk of gestation and that prenatal diagnosis by CV biopsy is possible.
MESH: Amniocentesis-; Amniotic-Fluid-enzymology; Amniotic-Fluid-metabolism; Case-Control-Studies; Cholesterol-metabolism; Chorionic-Villi-enzymology; Chorionic-Villi-metabolism; Chorionic-Villi-Sampling; Gestational-Age; Pregnancy-; Smith-Lemli-Opitz-Syndrome-metabolism
MESH: *Oxidoreductases-deficiency; *Prenatal-Diagnosis; *Smith-Lemli-Opitz-Syndrome-diagnosis; *Smith-Lemli-Opitz-Syndrome-enzymology
TG: Female; Human
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 57-88-5
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Cholesterol
AN: 96298554
UD: 9612
MEDLINE EXPRESS (R) 1992-1996 50 of 60
TI: Detection of defective 3 beta-hydroxysterol delta 7-reductase activity in cultured human fibroblasts: a method for the diagnosis of Smith-Lemli-Opitz syndrome.
AU: Lund-E; Starck-L; Venizelos-N
AD: Karolinska Institute, Division of Clinical Chemistry, Huddinge Hospital, Sweden.
SO: J-Inherit-Metab-Dis. 1996; 19(1): 59-64
ISSN: 0141-8955
PY: 1996
LA: ENGLISH
CP: NETHERLANDS
AB: Patients with the autosomal recessive disorder Smith-Lemli-Optiz syndrome (SLO) have recently been shown to have markedly increased tissue levels of certain cholesterol biosynthesis intermediates, most notably 7-dehydrocholesterol. The findings strongly suggest a block in the step that catalyses reduction of 7-dehydrocholesterol to cholesterol. The accumulation of 7-dehydrocholesterol can generally easily be detected in serum by gas chromatography-mass spectrometry. However, it could not be totally ruled out that SLO patients with less severe enzyme defects could escape detection by this method. A more direct way of diagnosing a defect in 7-dehydrocholesterol reduction would be to assay the conversion of 7-dehydrocholesterol to cholesterol in cultured fibroblasts from patients with suspected SLO. In the present work, an assay for the conversion of [3H]lathosterol to [3H]cholesterol in cultured human fibroblasts is described. Lathosterol is the immediate precursor of 7-dehydrocholesterol in the cholesterol biosynthetic pathway and was chosen for the assay instead of 7-dehydrocholesterol owing to the difficulty in preparation and handling of the latter compound. Fibroblasts from control subjects converted [3H]lathosterol to [3H]cholesterol efficiently, whereas in fibroblasts from SLO patients the conversion did not go beyond 7-dehydrocholesterol. It is concluded that the present method is useful for the diagnosis of SLO.
MESH: Cells,-Cultured; Cholesterol-metabolism; Chromatography,-High-Pressure-Liquid; Culture-Media; Fibroblasts-enzymology; Mass-Fragmentography; Prenatal-Diagnosis; Skin-cytology; Skin-enzymology
MESH: *Oxidoreductases-deficiency; *Smith-Lemli-Opitz-Syndrome-diagnosis; *Smith-Lemli-Opitz-Syndrome-enzymology
TG: Human
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 0; 57-88-5; 80-99-9
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Culture-Media; Cholesterol; lathosterol
AN: 96255072
UD: 9612
MEDLINE EXPRESS (R) 1992-1996 51 of 60
TI: [Smith-Lemli-Opitz syndrome; a special defect in cholesterol metabolism]
TO: Het Smith-Lemli-Opitz-syndroom; een bijzonder defect in het cholesterolmetabolisme.
AU: Aalfs-CM; Hennekam-RC; Wanders-RJ; Jira-PE; Pilon-JW; Wijburg-FA
AD: Instituut voor Antropogenetica. afd. Klinische Genetica, Amsterdam.
SO: Ned-Tijdschr-Geneeskd. 1996 Jul 13; 140(28): 1463-6
ISSN: 0028-2162
PY: 1996
LA: DUTCH; NON-ENGLISH
CP: NETHERLANDS
AB: In a male neonate dysmaturity, microcephalia, a high nasal bridge, a long philtrum, broad dental ridges, schisis of the palatum molle, retrognathia, a small penis with a chorda, a small scrotum, bilateral inguinal hernia and bilateral syndactyly of the second and third toes were observed. The presence of the Smith-Lemli-Opitz (SLO) syndrome was suspected. By gas chromatography a severely decreased plasma cholesterol level (0.27 mmol/l) was found and an increased plasma 7-dehydrocholesterol level (0.24 mmol/l). The SLO syndrome is caused by a block in the cholesterol biosynthesis due to the autosomal recessive deficiency of 7-dehydrocholesterol reductase. The patient's condition improved with use of a cholesterol-enriched diet.
MESH: Abnormalities,-Multiple; Cholesterol-biosynthesis; Chromatography,-Gas; Dehydrocholesterols-blood; English-Abstract; Genes,-Recessive; Infant,-Newborn; Oxidoreductases-genetics
MESH: *Cholesterol-blood; *Smith-Lemli-Opitz-Syndrome-blood
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 0; 434-16-2; 57-88-5
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 96339166
UD: 9612
MEDLINE EXPRESS (R) 1992-1996 52 of 60
TI: Smith-Lemli-Opitz syndrome and malignant hyperthermia [letter; comment]
CM: Comment on: Anesth Analg 1995 Mar;80(3):606-8
AU: Haji-Michael-PG; Hatch-DL
SO: Anesth-Analg. 1996 Jul; 83(1): 200
ISSN: 0003-2999
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
MESH: *Anesthesia-adverse-effects; *Malignant-Hyperthermia-etiology; *Smith-Lemli-Opitz-Syndrome
TG: Human
PT: COMMENT; LETTER
AN: 96259423
UD: 9610
SB: AIM
MEDLINE EXPRESS (R) 1992-1996 53 of 60
TI: Identification of 19-nor-5,7,9(10)-cholestatrien-3 beta-ol in patients with Smith-Lemli-Opitz syndrome.
AU: Batta-AK; Salen-G; Tint-GS; Shefer-S
AD: Department of Medicine, University of Medicine and Dentistry-New Jersey Medical School, Newark, USA.
SO: J-Lipid-Res. 1995 Nov; 36(11): 2413-8
ISSN: 0022-2275
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: We have identified the third unknown sterol in the plasma and tissues of Smith-Lemli-Opitz homozygotes as 19-nor-5,7,9(10)-cholestatrien-3 beta-ol. The structure was established from capillary gas-liquid chromatography retention index and characteristic fragmentation pattern by mass spectrometry that were identical to a synthetic reference standard. Evidence is presented that 19-nor-5,7,9(10)-cholestatrien-3 beta-ol is not an artifact formed during the chemical isolation of the relatively unstable 7-dehydrocholesterol. It is possible that 19-nor-5,7,9(10)-cholestatrien-3 beta-ol may contribute to the clinical abnormalities in patients with Smith-Lemli-Opitz syndrome.
MESH: Cholestadienols-blood; Cholestenes-blood; Cholesterol-metabolism; Dehydrocholesterols-blood; Molecular-Structure; Smith-Lemli-Opitz-Syndrome-blood; Spectrum-Analysis,-Mass
MESH: *Cholestadienols-metabolism; *Cholestenes-analysis; *Dehydrocholesterols-metabolism; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK18707DKNIDDK; HD31932HDNICHD; HL17818HLNHLBI
RN: 0; 0; 0; 0; 434-16-2; 57-88-5; 70741-38-7
NM: Cholestadienols; Cholestenes; Dehydrocholesterols; 19-nor-5,7,9(10)-cholestatrien-3-ol; 7-dehydrocholesterol; Cholesterol; cholesta-5,8-dien-3-beta-ol
AN: 96229388
UD: 9610
MEDLINE EXPRESS (R) 1992-1996 54 of 60
TI: Prenatal diagnosis of Smith-Lemli-Opitz syndrome is possible by measurement of 7-dehydrocholesterol in amniotic fluid.
AU: Dallaire-L; Mitchell-G; Giguere-R; Lefebvre-F; Melancon-SB; Lambert-M
AD: Service de Genetique Medicale, Hopital Sainte-Justine, Montreal, Quebec, Canada.
SO: Prenat-Diagn. 1995 Sep; 15(9): 855-8
ISSN: 0197-3851
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: Amniocentesis was performed at 17.3 weeks in a pregnancy with severe intrauterine growth retardation. Cytogenetic studies on amniocytes were normal, 46,XX, and the pregnancy was continued. The diagnosis of Smith-Lemli-Opitz syndrome was suspected in the neonatal period and confirmed by the presence of 7-dehydrocholesterol (7-DHC) in the plasma (0.4 mmol/l, normal = not detectable) associated with a low total cholesterol concentration (0.4 mmol/l, normal = 2.56 +/- 0.23). Retrospective analysis of the amniotic fluid sample revealed an elevated level of 7-DHC (0.022 mmol/l; normal = undetectable). Therefore measurement of 7-DHC levels in amniotic fluid during the second trimester of pregnancy is useful for the prenatal diagnosis of Smith-Lemli-Opitz syndrome in families at risk and should be considered in cases of severe growth retardation of unknown aetiology for which amniotic fluid is available and in which a normal chromosomal pattern in amniocytes is present.
MESH: Adult-; Cholesterol-blood; Chromatography,-Gas; Dehydrocholesterols-blood; Fetal-Growth-Retardation-etiology; Pregnancy-; Pregnancy-Trimester,-Second; Smith-Lemli-Opitz-Syndrome-metabolism; Spectrum-Analysis,-Mass
MESH: *Amniocentesis-; *Amniotic-Fluid-chemistry; *Dehydrocholesterols-analysis; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Case-Report; Female; Human
PT: JOURNAL-ARTICLE
RN: 0; 434-16-2; 57-88-5
NM: Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 96117617
UD: 9605
MEDLINE EXPRESS (R) 1992-1996 55 of 60
TI: Increased first trimester nuchal translucency as a prenatal manifestation of Smith-Lemli-Opitz syndrome.
AU: Hyett-JA; Clayton-PT; Moscoso-G; Nicolaides-KH
AD: Harris Birthright Research Centre for Fetal Medicine, Kings College Hospital Medical School, London, England.
SO: Am-J-Med-Genet. 1995 Sep 25; 58(4): 374-6
ISSN: 0148-7299
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Routine ultrasound examination at 11 weeks of gestation in a woman with no family history of genetic disease demonstrated increased accumulation of fluid in the fetal nuchal region. In view of the association of this defect with chromosomal abnormalities, fetal karyotyping was performed by chorion villus sampling and this demonstrated a normal 46,XY karyotype. Subsequent scans showed resolution of the nuchal fluid, and at the 20-week scan the fetal genitalia appeared to be female. Fetal blood sampling confirmed a normal male karyotype and fetoscopy confirmed the presence of female external genitalia. The parents elected to terminate the pregnancy, and postmortem findings were indicative of Smith-Lemli-Opitz syndrome. This was confirmed by the finding of increased levels of 7-dehydrocholesterol in cultured skin fibroblasts.
MESH: Adult-; Cells,-Cultured; Chorionic-Villi-Sampling; Dehydrocholesterols-analysis; Fetal-Diseases-embryology; Fetoscopy-; Fibroblasts-chemistry; Karyotyping-; Oxidoreductases-deficiency; Pregnancy-; Smith-Lemli-Opitz-Syndrome-embryology
MESH: *Fetal-Diseases-ultrasonography; *Neck-ultrasonography; *Smith-Lemli-Opitz-Syndrome-ultrasonography
TG: Case-Report; Female; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 1.; EC 1.3.1.21; 0; 434-16-2
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Dehydrocholesterols; 7-dehydrocholesterol
AN: 96087277
UD: 9604
MEDLINE EXPRESS (R) 1992-1996 56 of 60
TI: Quantification of 7-dehydrocholesterol in plasma and amniotic fluid by liquid chromatography/particle beam-mass spectrometry as a biochemical diagnostic marker for the Smith-Lemli-Opitz syndrome.
AU: Sattler-W; Leis-HJ; Kostner-GM; Malle-E
AD: Institute of Medical Biochemistry, Karl-Franzens University Graz, Austria.
SO: Rapid-Commun-Mass-Spectrom. 1995; 9(13): 1288-92
ISSN: 0951-4198
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: The qualitative and quantitative determination of cholesterol and 7-dehydrocholesterol (7-DHC) in plasma as a biochemical diagnostic marker for the Smith-Lemli-Opitz syndrome by liquid chromatography/particle beam interface-mass spectrometry (LC/PB-MS) is presented. Baseline separation of cholesterol and 7-DHC is achieved on a silica column with hexane+ethanol (99: 1 v/v) as mobile phase within a 10 min analysis. Recoveries of cholesterol and 7-DHC in a simple two-phase extraction system are nearly 100%. The absolute limit of detection using LC/PB-MS is approximately 10 ng. The method presented allows extraction, analysis and quantification of cholesterol and 7-DHC within 15 min without the necessity of sample derivatization.
MESH: Biological-Markers; Cholesterol-blood; Chromatography,-Liquid; Dehydrocholesterols-blood; Pregnancy-; Smith-Lemli-Opitz-Syndrome-blood; Spectrum-Analysis,-Mass
MESH: *Amniotic-Fluid-chemistry; *Dehydrocholesterols-analysis; *Smith-Lemli-Opitz-Syndrome-diagnosis
TG: Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 434-16-2; 57-88-5
NM: Biological-Markers; Dehydrocholesterols; 7-dehydrocholesterol; Cholesterol
AN: 96064462
UD: 9604
MEDLINE EXPRESS (R) 1992-1996 57 of 60
TI: Defective conversion of 7-dehydrocholesterol to cholesterol in cultured skin fibroblasts from Smith-Lemli-Opitz syndrome homozygotes.
AU: Honda-A; Tint-GS; Salen-G; Batta-AK; Chen-TS; Shefer-S
AD: Department of Medicine, Veterans Affairs Medical Center, East Orange, NJ 07018, USA.
SO: J-Lipid-Res. 1995 Jul; 36(7): 1595-601
ISSN: 0022-2275
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The Smith-Lemli-Opitz syndrome is a common birth defect syndrome characterized biochemically by low plasma cholesterol levels and high concentrations of the cholesterol precursor 7-dehydrocholesterol. The present study was undertaken to prove that the enzyme defect is at the step in which 7-dehydrocholesterol is converted into cholesterol and to establish a new biochemical method for the diagnosis of this disease. We assayed the latter part of the cholesterol biosynthetic pathway by incubating [3H]lathosterol (the immediate precursor of 7-dehydrocholesterol) with cultured skin fibroblasts from 15 homozygous patients, 14 obligate heterozygous parents, and 8 controls, and measuring its conversion to 7-dehydrocholesterol and cholesterol. The formation of cholesterol from lathosterol in parents was not significantly different from that in controls. In contrast, cells from patients made very little cholesterol (P < 0.0001, patients vs. parents or vs. controls) but readily converted lathosterol to 7-dehydrocholesterol. The defect was especially profound in a subgroup of 8 of the most severely clinically affected patients, as virtually no label was detected in the cholesterol fraction. These results provide compelling evidence that 1) this disease is caused by a primary defect in 7-dehydrocholesterol delta 7-reductase, an essential enzyme in the biosynthesis of cholesterol; 2) the most clinically severe form of the syndrome may be associated with the most inhibited enzyme; and 3) the enzyme lathosterol 5-desaturase that converts lathosterol to 7-dehydrocholesterol is fully intact. The present method using fibroblast and amniocyte cultures establishes it as a useful procedure for the biochemical diagnosis of this syndrome.
MESH: Adolescence-; Adult-; Cells,-Cultured; Child-; Child,-Preschool; Oxidoreductases-deficiency; Oxidoreductases-metabolism; Skin-metabolism; Tritium-
MESH: *Cholesterol-metabolism; *Dehydrocholesterols-metabolism; *Fibroblasts-metabolism; *Smith-Lemli-Opitz-Syndrome-metabolism
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK18707DKNIDDK; HL17818HLNHLBI; HD31932HDNICHD
RN: EC 1.; EC 1.3.1.21; EC 1.3.3.2; 0; 10028-17-8; 434-16-2; 57-88-5; 80-99-9
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; lathosterol-delta-5-dehydrogenase; Dehydrocholesterols; Tritium; 7-dehydrocholesterol; Cholesterol; lathosterol
AN: 96003007
UD: 9602
MEDLINE EXPRESS (R) 1992-1996 58 of 60
TI: Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes.
AU: Shefer-S; Salen-G; Batta-AK; Honda-A; Tint-GS; Irons-M; Elias-ER; Chen-TC; Holick-MF
AD: UMD-New Jersey Medical School, Newark 07103, USA.
SO: J-Clin-Invest. 1995 Oct; 96(4): 1779-85
ISSN: 0021-9738
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: We investigated the enzyme defect in late cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome, a recessively inherited developmental disorder characterized by facial dysmorphism, mental retardation, and multiple organ congenital anomalies. Reduced plasma and tissue cholesterol with increased 7-dehydrocholesterol concentrations are biochemical features diagnostic of the inherited enzyme defect. Using isotope incorporation assays, we measured the transformation of the precursors, [3 alpha- 3H]lathosterol and [1,2-3H]7-dehydrocholesterol into cholesterol by liver microsomes from seven controls and four Smith-Lemli-Opitz homozygous subjects. The introduction of the double bond in lathosterol at C-5[6] to form 7-dehydrocholesterol that is catalyzed by lathosterol-5-dehydrogenase was equally rapid in controls and homozygotes liver microsomes (120 +/- 8 vs 100 +/- 7 pmol/mg protein per min, P = NS). In distinction, the reduction of the double bond at C-7 [8] in 7-dehydrocholesterol to yield cholesterol catalyzed by 7-dehydrocholesterol-delta 7-reductase was nine times greater in controls than homozygotes microsomes (365 +/- 23 vs 40 +/- 4 pmol/mg protein per min, P < 0.0001). These results demonstrate that the pathway of lathosterol to cholesterol in human liver includes 7-dehydrocholesterol as a key intermediate. In Smith-Lemli-Opitz homozygotes, the transformation of 7-dehydrocholesterol to cholesterol by hepatic microsomes was blocked although 7-dehydrocholesterol was produced abundantly from lathosterol. Thus, lathosterol 5-dehydrogenase is equally active which indicates that homozygotes liver microsomes are viable. Accordingly, microsomal 7-dehydrocholesterol-delta 7-reductase is inherited abnormally in Smith-Lemli-Opitz homozygotes.
MESH: Cholesterol-biosynthesis; Cholesterol-metabolism; Homozygote-; Oxidoreductases-metabolism; Smith-Lemli-Opitz-Syndrome-genetics
MESH: *Microsomes,-Liver-enzymology; *Oxidoreductases-antagonists-and-inhibitors; *Smith-Lemli-Opitz-Syndrome-enzymology
TG: Female; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL17818HLNHLBI; DK26756DKNIDDK
RN: EC 1.; EC 1.3.1.21; 57-88-5; 80-99-9
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Cholesterol; lathosterol
AN: 96013638
UD: 9601
SB: AIM
MEDLINE EXPRESS (R) 1992-1996 59 of 60
TI: Treatment of the cholesterol biosynthetic defect in Smith-Lemli-Opitz syndrome reproduced in rats by BM 15.766.
AU: Xu-G; Salen-G; Shefer-S; Ness-GC; Chen-TS; Zhao-Z; Salen-L; Tint-GS
AD: Department of Veterans Affairs Medical Center, East Orange, New Jersey, USA.
SO: Gastroenterology. 1995 Oct; 109(4): 1301-7
ISSN: 0016-5085
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: BACKGROUND & AIMS: The Smith-Lemli-Opitz syndrome is a recessive inherited disorder characterized by neurological developmental defects and dysmorphic features with a defect in cholesterol synthesis at the conversion of 7-dehydrocholesterol to cholesterol. BM 15.766 inhibits 7-dehydrocholesterol-delta 7-reductase and reproduces the biochemical defect. The aim of this study was to investigate the effects of cholesterol, cholic acid, and lovastatin feeding on rats fed BM 15.766. METHODS: Plasma cholesterol and 7-dehydrocholesterol concentrations were related to the hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. RESULTS: With the inhibitor treatment, plasma cholesterol concentrations decreased 67%; 7-dehydrocholesterol concentrations increased from trace to 17 mg/dL; and hepatic HMG-CoA reductase activity and messenger RNA levels were stimulated 74% and two times, respectively. In inhibitor-treated rats, feeding cholesterol increased plasma cholesterol concentrations 3.7 times, decreased 7-dehydrocholesterol concentrations 88%, and reduced elevated HMG-CoA reductase activity and messenger RNA levels 74% and 49%. Feeding cholic acid increased plasma cholesterol without reducing 7-dehydrocholesterol concentrations. The combination of cholic acid and cholesterol enhanced plasma cholesterol 9.5 times without decreasing 7-dehydrocholesterol levels. Feeding lovastatin depressed plasma cholesterol further without reducing 7-dehydrocholesterol levels. CONCLUSIONS: Cholesterol is essential to correct abnormal cholesterol synthesis induced by BM 15.766 in rats by expanding the pool and inhibiting HMG-CoA reductase. Neither cholic acid nor lovastatin are effective separately, but cholic acid plus cholesterol may offer some additional benefit.
MESH: Acyl-Coenzyme-A-analysis; Cholesterol-biosynthesis; Cholesterol-blood; Dehydrocholesterols-blood; Disease-Models,-Animal; Liver-enzymology; Microsomes,-Liver-enzymology; Oxidoreductases-antagonists-and-inhibitors; Piperazines-pharmacology; Rats-; Rats,-Sprague-Dawley; Smith-Lemli-Opitz-Syndrome-chemically-induced; Smith-Lemli-Opitz-Syndrome-metabolism
MESH: *Cholesterol-therapeutic-use; *Cholic-Acids-therapeutic-use; *Lovastatin-therapeutic-use; *Smith-Lemli-Opitz-Syndrome-drug-therapy
TG: Animal; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL17818HLNHLBI; HL18094HLNHLBI; DK18707DKNIDDK
RN: EC 1.; EC 1.3.1.21; 0; 0; 0; 0; 1553-55-5; 434-16-2; 57-88-5; 75330-75-5; 81-25-4; 86621-92-3
NM: Oxidoreductases; 7-dehydrocholesterol-reductase; Acyl-Coenzyme-A; Cholic-Acids; Dehydrocholesterols; Piperazines; 3-hydroxy-3-methylglutaryl-coenzyme-A; 7-dehydrocholesterol; Cholesterol; Lovastatin; cholic-acid; BM-15766
AN: 96029334
UD: 9601
SB: AIM
MEDLINE EXPRESS (R) 1992-1996 60 of 60
TI: [Genetic morphological fatal syndrome. Smith-Lemli-Opitz syndrome]
TO: Genetisch-morphologische Letalsyndrome. Das Smith-Lemli-Opitz-Syndrome.
AU: Henkel-KE; Pfeiffer-RA; Stoss-H
AD: Institut fur Humangenetik, Friedrich-Alexander-Universitat Erlangen-Nurnberg.
SO: Pathologe. 1993 Mar; 14(2): 91-2
ISSN: 0172-8113
PY: 1993
LA: GERMAN; NON-ENGLISH
CP: GERMANY
MESH: Abnormalities,-Multiple-pathology; Chromosome-Abnormalities-genetics; Diagnosis,-Differential; Genes,-Lethal-genetics; Genes,-Recessive-genetics; Hypospadias-pathology; Infant,-Newborn; Syndrome-
MESH: *Abnormalities,-Multiple-genetics; *Facial-Bones-abnormalities; *Fingers-abnormalities; *Hypospadias-genetics; *Skull-abnormalities; *Toes-abnormalities
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 93226596
UD: 9307