title: 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.affiliation: 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
authors.forename: D
authors.initials: D
authors.lastname: Haas
authors.forename: S F
authors.initials: SF
authors.lastname: Garbade
authors.forename: C
authors.initials: C
authors.lastname: Vohwinkel
authors.forename: N
authors.initials: N
authors.lastname: Muschol
authors.forename: F K
authors.initials: FK
authors.lastname: Trefz
authors.forename: J M
authors.initials: JM
authors.lastname: Penzien
authors.forename: J
authors.initials: J
authors.lastname: Zschocke
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: P
authors.initials: P
authors.lastname: Burgard
mesh_terms: 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
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin