Effects of cholesterol and simvastatin treatment in patients with Smith–Lemli–Opitz syndrome (SLOS)

• DOI: 10.1007/s10545-007-0537-7
• Publication Date: 2007-05-13T08:37:50Z
• Authors: D. Haas; S. F. Garbade; C. Vohwinkel; N. Muschol; F. K. Trefz; J. M. Penzien; J. Zschocke; G. F. Hoffmann; P. Burgard
• Keywords: Male; 0301 basic medicine; Simvastatin; Genotype; Smith-Lemli-Opitz Syndrome; 3. Good health; Cohort Studies; 03 medical and health sciences; Cholesterol; Enteral Nutrition; Dietary Supplements; Humans; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Child

SummarySmith–Lemli–Opitz syndrome (SLOS) is a malformation syndrome caused by deficiency of 7‐dehydrocholesterol reductase catalysing the last step of cholesterol biosynthesis. This results in an accumulation of 7‐ and 8‐dehydrocholesterol (7+8–DHC) and, in most patients, a deficiency of cholesterol. Current therapy consists of dietary cholesterol supplementation, which raises plasma cholesterol levels, but clinical effects have been reported in only a few patients. Hydroxymethylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors were shown to reduce 7+8–DHC levels and increase cholesterol concentrations in two small trials with divergent clinical outcome. This retrolective study evaluates the effects of cholesterol only and of cholesterol plus the HMG‐CoA reductase inhibitor simvastatin on plasma sterols in 39 SLOS patients and on anthropometric measures in 20 SLOS patients. Cholesterol as well as additional simvastatin decreased the plasma (7+8–DHC)/cholesterol ratio. However, the mechanism leading to the decreasing ratio was different. Whereas it was due to an increasing cholesterol concentration in the cholesterol‐only cohort, a decreasing 7+8–DHC concentration was demonstrated in the cohort receiving additional simvastatin. We could not confirm a positive effect of simvastatin treatment on anthropometric measures or behaviour, as previously reported.