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 3β-hydroxysteroid-Δ5-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.

DOI: 10.1086/342668
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