To determine whether type I and the more severe type II variant of Smith-Lemli-Opitz syndrome have the same metabolic defect and to learn which plasma sterol measurements best predict survival.

Plasma sterols were measured in 33 individuals (24 type I, 9 type II) with a clinical diagnosis of the syndrome.

Cholesterol levels were abnormally low (61 ± 34 mg/dl) in type I subjects, whereas concentrations of the cholesterol precursor 7-dehydrocholesterol and its isomer 8-dehydrocholesterol were elevated 40- to 10,000-fold. Plasma cholesterol levels were significantly lower and total dehydrocholesterol levels higher in type II than in type I. Six children with the type II variant died by 13 weeks with mean plasma cholesterol levels 6.2 ± 3.1 mg/dl, versus 17 ± 11 mg/dl in the three surviving children with type II (p <0.05). No child with a cholesterol level 7 mg/dl or less lived longer than 13 weeks.

Patients with type I and type II variants of Smith-Lemli-Opitz syndrome have markedly reduced activity of the enzyme that converts 7-dehydrocholesterol to cholesterol, but the extent of the block is far more complete in type II. Survival correlates strongly with higher plasma cholesterol concentrations. (J PEDIATR 1995;127:82-7)