%0 Journal Article %1 haas.garbade.ea:effects %A Haas, D. %A Garbade, S. F. %A Vohwinkel, C. %A Muschol, N. %A Trefz, F. K. %A Penzien, J. M. %A Zschocke, J. %A Hoffmann, G. F. %A Burgard, P. %D 2007 %K /&/ Child; Cholesterol, Cohort Dietary Enteral Female; Genotype; Humans; Hydroxymethylglutaryl-CoA Inhibitors, Male; Nutrition; Reductase Simvastatin, Smith-Lemli-Opitz Studies; Supplements; Syndrome, administration dosage/therapeutic drug sfg therapeutic therapy/genetics use; %N 3 %P 375--387 %R 10.1007/s10545-007-0537-7 %T Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS). %U http://dx.doi.org/10.1007/s10545-007-0537-7 %V 30 %X 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.

@article{haas.garbade.ea:effects, 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.}, added-at = {2017-04-01T10:34:58.000+0200}, author = {Haas, D. and Garbade, S. F. and Vohwinkel, C. and Muschol, N. and Trefz, F. K. and Penzien, J. M. and Zschocke, J. and Hoffmann, G. F. and Burgard, P.}, biburl = {https://www.bibsonomy.org/bibtex/245f4b10e66eb98b07e5535b2c0f6b48f/sveng}, doi = {10.1007/s10545-007-0537-7}, institution = {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}, interhash = {a2a2c80786fa3c43d8636c635675fa67}, intrahash = {45f4b10e66eb98b07e5535b2c0f6b48f}, journaltitle = {Journal of Inherited Metabolic Disease}, keywords = {/&/ Child; Cholesterol, Cohort Dietary Enteral Female; Genotype; Humans; Hydroxymethylglutaryl-CoA Inhibitors, Male; Nutrition; Reductase Simvastatin, Smith-Lemli-Opitz Studies; Supplements; Syndrome, administration dosage/therapeutic drug sfg therapeutic therapy/genetics use;}, month = Jun, number = 3, owner = {sfg}, pages = {375--387}, pmid = {17497248}, shortjournal = {J Inherit Metab Dis}, timestamp = {2017-04-01T10:35:16.000+0200}, title = {Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome ({SLOS}).}, url = {http://dx.doi.org/10.1007/s10545-007-0537-7}, volume = 30, year = 2007 }