Markedly increased tissue concentrations of 7-dehydrocholesterol combined with low levels of cholesterol are characteristic of the Smith-Lemli-Opitz syndrome

G. S. Tint*, M. Seller, R. Hughes-Benzie, A. K. Batta, S. Shefer, D. Genest, M. Irons, E. Elias, G. Salen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

The Smith-Lemli-Opitz syndrome is an autosomal recessive birth defect (frequency 1:20,000-1:40,000) that results in profound mental retardation, physical deformities, and failure to thrive. It is characterized biochemically by low plasma cholesterol and greatly elevated levels of two dehydrocholesterols, one of which is the cholesterol precursor 7- dehydrocholesterol. To determine whether the block in cholesterol biosynthesis affects tissue sterols, we assayed several organs from two affected individuals, a female who died at 27 hours and a 20-week male fetus. Cholesterol concentrations in abdominal wall, adrenal gland, and kidney from two or three unaffected thrusts, who served as controls, averaged 2.0, 1.5, and 1.4 mg/g wet weight, compared to 0.08, 0.44, and 0.14, respectively, for the homozygous fetus. Cerebral cortex cholesterol concentrations were 2.2 mg/g for two 20-22-week fetal controls but only 0.21 and 0.09 mg/g, respectively, for the homozygous child and fetus. Similarly, tissue cholesterol levels were abnormally low in the homozygous child being less than 1 mg/g in liver, adipose, thymus, muscle, and adrenal and 6.2 mg/dl in plasma. Dehydrocholesterols could not be detected by conventional means in any controls but were elevated enough in tissues from affected individuals to make total sterol concentrations nearly nor mal. These results suggest that a defect in 3β-hydroxysterol Δ7-reductase leads to both a profound lack of cholesterol and its replacement by dehydrocholesterols. Such a combination may be lethal in the most severely affected individuals.

Original languageEnglish (US)
Pages (from-to)89-95
Number of pages7
JournalJournal of lipid research
Volume36
Issue number1
StatePublished - 1995
Externally publishedYes

Keywords

  • birth defects
  • capillary gas chromatography
  • cholesta-5,8-dien-3β- ol
  • cholesterol biosynthesis
  • mass spectroscopy
  • mental retardation
  • plasma sterols

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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