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Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome
The Italian Journal of Gastroenterology
|December 1, 1995
Summary
Smith-Lemli-Opitz syndrome is an inherited disorder causing low cholesterol and high 7-dehydrocholesterol. This biochemical abnormality in patients can be replicated in rats using a 7-dehydrocholesterol 7-reductase inhibitor.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Smith-Lemli-Opitz syndrome (SLOS) is a rare inherited disorder.
- The syndrome is characterized by a deficiency in cholesterol synthesis.
- Elevated levels of the precursor 7-dehydrocholesterol are observed in SLOS patients.
Purpose of the Study:
- To investigate the biochemical basis of Smith-Lemli-Opitz syndrome.
- To identify the specific enzyme defect responsible for the observed sterol abnormalities.
- To establish an animal model for studying SLOS.
Main Methods:
- Plasma sterol concentrations were measured in SLOS homozygotes and heterozygotes.
- Rats were treated with BM 15.766, a competitive inhibitor of 7-dehydrocholesterol 7-reductase.
- Sterol profiles were analyzed to compare findings between patients and the animal model.
Main Results:
- Homozygotes with SLOS exhibited low plasma cholesterol and significantly elevated 7-dehydrocholesterol.
- Rats treated with BM 15.766 showed similar biochemical profiles: low cholesterol and high 7-dehydrocholesterol.
- Clinically normal heterozygotes and control subjects had only trace amounts of 7-dehydrocholesterol.
Conclusions:
- The Smith-Lemli-Opitz syndrome results from an inherited defect in the enzyme 7-dehydrocholesterol 7-reductase.
- This enzymatic defect leads to cholesterol deficiency and 7-dehydrocholesterol accumulation.
- BM 15.766 treatment in rats effectively models the biochemical phenotype of SLOS.