Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase

Am J Hum Genet. 2002 Oct;71(4):952-8. doi: 10.1086/342668. Epub 2002 Aug 20.

Abstract

We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / enzymology*
  • Abnormalities, Multiple / metabolism
  • Cholesterol / metabolism*
  • Humans
  • Infant
  • Intellectual Disability / enzymology*
  • Intellectual Disability / metabolism
  • Oxidoreductases / deficiency
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Oxidoreductases Acting on CH-CH Group Donors*
  • Syndrome

Substances

  • lathosterol delta-5-dehydrogenase
  • lathosterol
  • Cholesterol
  • Oxidoreductases
  • Oxidoreductases Acting on CH-CH Group Donors

Associated data

  • OMIM/118450
  • OMIM/207410
  • OMIM/215140
  • OMIM/270400
  • OMIM/302960
  • OMIM/308050
  • OMIM/602398