Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS).
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.
Haas
D
D
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Hospital for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, D-69120, Heidelberg, Germany. dorothea.haas@med.uni-heidelberg.de
Garbade
S F
SF
Vohwinkel
C
C
Muschol
N
N
Trefz
F K
FK
Penzien
J M
JM
Zschocke
J
J
Hoffmann
G F
GF
Burgard
P
P
D002648:Child; D002784:Cholesterol / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D019587:Dietary Supplements; D004750:Enteral Nutrition; D005260:Female; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D019821:Simvastatin / Q000627:therapeutic use*; D019082:Smith-Lemli-Opitz Syndrome / Q000188:drug therapy* / Q000235:genetics
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin