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

Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol m etabolism in which 7- and 8-dehydrocholesterols are accumulated in blood an d tissues. Diagnosis of SLOS and other disorders in cholesterol metabolism (eg, cerebrotendinous xanthomatosis, phytosterolemia, desmosterolosis, and X-linked dominant Conradi-Hunermann-Happle syndrome) can be performed by ga s-liquid chromatographic analysis of serum sterols. To elucidate their invo lvement in developmental disability, we evaluated serum sterols in two stud y 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 th e 49 children. Seven additional adult cases (type I) with a wide range of c linical features and the serum sterol abnormalities characteristic of SLOS were detected from among the developmentally disabled subjects. The frequen cy of SLOS in the latter group was relatively high (7 in 322). No other her editary sterol disorders were found, but two subgroups with low serum chole sterol precursor sterols and high serum plant sterols were identified. Seve ral subjects, including the 7 SLOS patients, used ample medication and had abnormalities in serum sterol concentrations. Thus, among the subjects taki ng melperone, a high serum Delta (8)-cholesterol level suggests an interfer ence by the drug with cholesterol synthesis. Our results emphasize the impo rtance of analyzing the serum sterols of developmentally disabled subjects to diagnose SLOS and of finding putative undiagnosed disorders in sterol me tabolism associated with these clinical conditions.