Simvastatin treatment in the SLO syndrome: a safe approach?

Soon after the discovery of reduced cholesterol synthesis in the Smith-Lemli-Opitz syndrome (SLOS), several trials with dietary supplementation were initiated with the aim of increasing cholesterol and reducing the de novo synthesis and accumulation of 7- and 8-dehydrocholesterol (DHC). Dietary cholesterol raises cholesterol levels in the circulation with only marginal effects on levels of DHC. Photosensitivity and polyneuropathy have been reported to be improved by the treatment, but other effects have been difficult to evaluate. In order to see whether inhibition of hydroxymethylglutaryl CoA reductase is of benefit, two of our patients have been treated with simvastatin in addition to the long-term treatment with cholesterol and bile acids. Absolute as well as relative levels of DHC were reduced. In one patient, creatine kinase increased moderately after 2 months of treatment. In the other patient, the treatment had to be interrupted because of hepatotoxic side effects with a marked increase in alanine aminotransferase and aggravation of the hypocholesterolemia and photosensitivity. We conclude that even if the levels of accumulated intermediates can be reduced, treatment with a statin may be harmful in some patients with SLOS.