CORRELATION OF SEVERITY AND OUTCOME WITH PLASMA STEROL LEVELS IN VARIANTS OF THE SMITH-LEMLI-OPITZ SYNDROME

Objectives: To determine whether type I and the more severe type II va riant of Smith-Lemli-Opitz syndrome have the same metabolic defect and to learn which plasma sterol measurements best predict survival. Meth ods: Plasma sterols were measured in 33 individuals (24 type I, 9 type II) with a clinical diagnosis of the syndrome. Results: Cholesterol l evels were abnormally low (61 +/- 34 mg/dl) in type I subjects, wherea s concentrations of the cholesterol precursor 7-dehydrocholesterol and its isomer 8-dehydrocholesterol were elevated 40- to 10,000-fold. Pla sma cholesterol levels were significantly lower and total dehydrochole sterol 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 childr en with type II (p < 0.05), No child with a cholesterol level 7 mg/dl or less lived longer than 13 weeks. Conclusions: Patients with type an d type II variants of Smith-Lemli-Opitz syndrome have markedly reduced activity of the enzyme that converts 7-dehydrocholesterol to choleste rol, but the extent of the block is far more complete in type II. Surv ival correlates strongly with higher plasma cholesterol concentrations .