Smith-Lemli-Opitz syndrome and other sterol disorders among Finns with developmental disabilities

Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol metabolism in which 7- and 8-dehydrocholesterols are accumulated in blood and tissues. Diagnosis of SLOS and other disorders in cholesterol metabolism (eg, cerebrotendinous xanthomatosis, phytosterolemia, desmosterolosis, and X-linked dominant Conradi-Hünermann-Happle syndrome) can be performed by gas-liquid chromatographic analysis of serum sterols. To elucidate their involvement in developmental disability, we evaluated serum sterols in two study groups: developmentally disabled subjects in long-term care (N = 322) and newborns and young children (N = 49) with features of SLOS in the Finnish population of 5 million. Only 1 SLOS case (type II) was found from among the 49 children. Seven additional adult cases (type I) with a wide range of clinical features and the serum sterol abnormalities characteristic of SLOS were detected from among the developmentally disabled subjects. The frequency of SLOS in the latter group was relatively high (7 in 322). No other hereditary sterol disorders were found, but two subgroups with low serum cholesterol precursor sterols and high serum plant sterols were identified. Several subjects, including the 7 SLOS patients, used ample medication and had abnormalities in serum sterol concentrations. Thus, among the subjects taking melperone, a high serum delta8-cholestenol level suggests an interference by the drug with cholesterol synthesis. Our results emphasize the importance of analyzing the serum sterols of developmentally disabled subjects to diagnose SLOS and of finding putative undiagnosed disorders in sterol metabolism associated with these clinical conditions.