title: Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome.
abstract: BACKGROUND
  The Smith-Lemli-Opitz syndrome (frequency, 1:20,000 to 1:40,000) is defined by a constellation of severe birth defects affecting most organ systems. Abnormalities frequently include profound mental retardation, severe failure to thrive, and a high infant-mortality rate. The syndrome has heretofore been diagnosed only from its clinical presentation.
  
  
  METHODS
  Using capillary-column gas chromatography-mass spectrometry, we measured the sterol composition of plasma, erythrocytes, lens, cultured fibroblasts, and feces from five children with the syndrome (three girls and two boys).
  
  
  RESULTS
  Plasma cholesterol levels were abnormally low (8 to 101 mg per deciliter [0.20 to 2.60 mmol per liter]) in every patient, being well below the 5th percentile for age- and sex-matched controls. Concentrations of the cholesterol precursor 7-dehydrocholesterol (cholesta-5,7-dien-3 beta-ol), which was not detectable in most of our controls, were elevated (11 to 31 mg per deciliter) more than 2000-fold above normal and were similar to the levels of cholesterol in all tissues from all patients. An isomeric dehydrocholesterol with a structure similar to that of 7-dehydrocholesterol was also detected.
  
  
  CONCLUSIONS
  The combination of abnormally low plasma cholesterol levels and a high concentration of the cholesterol precursor 7-dehydrocholesterol points to a major block in cholesterol biosynthesis at the step in which the C-7(8) double bond of 7-dehydrocholesterol is reduced, forming cholesterol. The block may be sufficient to deprive an embryo or fetus of cholesterol and prevent normal development, whereas the incorporation of 7-dehydrocholesterol into all membranes may interfere with proper membrane function.
authors.affiliation: Department of Medicine, Veteran Affairs Medical Center, East Orange, N.J. 07018-1095.
authors.forename: G S
authors.initials: GS
authors.lastname: Tint
authors.forename: M
authors.initials: M
authors.lastname: Irons
authors.forename: E R
authors.initials: ER
authors.lastname: Elias
authors.forename: A K
authors.initials: AK
authors.lastname: Batta
authors.forename: R
authors.initials: R
authors.lastname: Frieden
authors.forename: T S
authors.initials: TS
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Salen
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood*; D000293:Adolescent; D001647:Bile Acids and Salts / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000096:biosynthesis*; D003684:Dehydrocholesterols / Q000032:analysis; D004912:Erythrocytes; D005183:Failure to Thrive; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital; D008297:Male; D008831:Microcephaly / Q000097:blood*; D013261:Sterols / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D003684:Dehydrocholesterols; D013261:Sterols; D002784:Cholesterol; C016705:7-dehydrocholesterol