Sterol profiling of amniotic fluid: a routine method for the detection of distal cholesterol synthesis deficit

Prenat Diagn. 2005 Nov;25(11):1000-6. doi: 10.1002/pd.1254.

Abstract

Objectives: Smith Lemli Opitz syndrome (SLOS) caused by a deficit of 3beta-hydroxysterol-Delta7 reductase was the first sterol deficit described with multiple malformations. The lack of specificity of many morphological abnormalities detected by ultrasound and their frequency have justified routine screening of amniotic fluid (AF) for sterols by GC-MS. The examination contributes to an improved knowledge of the sterol status in the fluid.

Methods: A series of sterol profiles is collated here. Accumulation of 7- and 8-dehydrocholesterol are diagnostic for SLOS. However, a number of other sterols have also been detected by GC-MS in control AF and their presence may be confusing.

Results and conclusions: In addition to cholesterol, the level of which varies as function of the gestational age, lathosterol is present together with trace amounts of 7- and 8-dehydrocholesterol and other precursors such as desmosterol, lanosterol, and dimethylsterol. Phytosterols are also present in 70% of AF samples that have been tested. Besides SLOS, GC-MS examination of amniotic fluid can detect various sterol deficits associated with malformations (lathosterolosis, desmosterolosis, X-linked chondrodysplasia, and particular Antley-Bixler syndrome). Practical conclusions support GC-MS as a routine method to investigate skeletal and central nervous system malformations.

Publication types

  • Evaluation Study

MeSH terms

  • Amniotic Fluid / chemistry*
  • Animals
  • Biomarkers / analysis
  • Cholestadienols / analysis
  • Cholesterol / analysis
  • Dehydrocholesterols / analysis
  • Gas Chromatography-Mass Spectrometry*
  • Gestational Age
  • Humans
  • Prenatal Diagnosis / methods*
  • Rats
  • Retrospective Studies
  • Smith-Lemli-Opitz Syndrome / diagnosis*
  • Sterols / analysis*

Substances

  • Biomarkers
  • Cholestadienols
  • Dehydrocholesterols
  • Sterols
  • cholesta-5,8-dien-3 beta-ol
  • Cholesterol
  • 7-dehydrocholesterol