SC4MOL Deficiency

SC4MOL deficiency is a new genetic disorder the in cholesterol biosynthesis pathway. It is characterized by significant accumulation of dimethyl and monomethyl sterols in the human body, which can be detected in blood, skin flakes or primary skin fibroblasts. Dr. Vockley has reported a mutation in the SC4MOL, a gene in the PSORS9 region on 4q32-34, as the cause of an autosomal recessive syndrome that includes psoriasis, arthralgias, microcephaly, congenital cataracts and developmental delay. A second affected child, identified at age 3½ years with milder dermal symptoms than the original patient, emphasizes that the disorder is likely to be heterogeneous. This gene encodes a sterol C4 methyl oxidase that catalyzes demethylation of methylsterols in the cholesterol synthesis pathway.

The methylsterols are meiosis-activating sterols (MAS) and are the first family of cholesterologenesis intermediates found to have functions other than de novo cholesterol biosynthesis. In vitro studies provide evidence that methylsterols also play a role in cell proliferation and immune regulation.

Through treatment with a statin and supplementation of cholesterol and bile acids, methylsterol levels in the initial patient normalized. In the two years following institution of therapy, the patient’s weight and growth improved dramatically with a growth velocity of 0.8 cm/month. Her height increased from below the 3rd percentile at 9 months of age and the 50th percentile for a 10½ year old at 13 years of age, to the 10th percentile for age by the time she reached 18.

These findings underscore the important extra-hepatic functions of C4 methyl oxidase and provide insights into the pathogenesis of cholesterologenesis disorders.

Principal Investigator
Gerard Vockley, MD, PhD

Last Update
August 13, 2010
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Last Update
August 13, 2010