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

Abstract

Smith-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.

• Authors: D Haas, S F Garbade, C Vohwinkel, N Muschol, F K Trefz, J M Penzien, J Zschocke, G F Hoffmann, P Burgard
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 30 Issue 3 Pg. 375-87 (Jun 2007) ISSN: 1573-2665 [Electronic] United States
• PMID: 17497248 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Cholesterol
• Simvastatin

Topics

• Child
• Cholesterol (administration & dosage, therapeutic use)
• Cohort Studies
• Dietary Supplements
• Enteral Nutrition
• Female
• Genotype
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Male
• Simvastatin (therapeutic use)
• Smith-Lemli-Opitz Syndrome (drug therapy, genetics)