Summary
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.
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Abbreviations
- CK:
-
creatine kinase
- 7-DHC:
-
7-dehydrocholesterol
- 8-DHC:
-
8-dehydrocholesterol
- DHCR7:
-
7-dehydrocholesterol reductase
- GC-MS:
-
gas chromatography-mass spectrometry
- HMG-CoA:
-
hydroxymethylglutaryl-coenzyme A
- HR:
-
cohort of patients with high (7+8–DHC)/cholesterol ratio
- LR:
-
cohort of patients with low (7+8–DHC)/cholesterol ratio
- MAD:
-
median absolute deviation
- MSHFBA:
-
N-methyl-N-trimethylsilylheptafluorobutyramide
- SLOS:
-
Smith–Lemli–Opitz syndrome
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Communicating editor: Michael Gibson
Competing interests: None declared
References to electronic databases: Smith–Lemli–Opitz syndrome (SLOS), OMIM 270400).
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Haas, D., Garbade, S.F., Vohwinkel, C. et al. Effects of cholesterol and simvastatin treatment in patients with Smith–Lemli–Opitz syndrome (SLOS). J Inherit Metab Dis 30, 375–387 (2007). https://doi.org/10.1007/s10545-007-0537-7
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DOI: https://doi.org/10.1007/s10545-007-0537-7