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.

Role of clozapine in the occurrence of chromosomal abnormalities in human bone-marrow cells in vivo and in cultured lymphocytes in vitro.

Bone-marrow chromosomes were examined from 38 mentally and physically retarded and two psychiatric patients who were being treated with a variety of neuropharmacologic drugs. Twenty of these patients used clozapine (Leponex). The clastogenic effects of clozapine in vitro were studied in the lymphocyte cultures of three patients--one free of hematologic disease and two who 6 months earlier had had agranulocytosis attributed to the use of clozapine. The mean frequency of cytogenetic abnormalities in the bone-marrow cells of patients who used clozapine was significantly increased (P less than 0.05). The two patients who had had agranulocytosis had a greater frequency of cytogenetic abnormalities in their cultured lymphocytes in vivo and in vitro than the patient free of hematologic disease. A clone with a 13/14 chromosome translocation was detected in one of the patients. As all patients received a number of drugs during the in vivo and in vitro studies no definite conclusions could be drawn regarding the role played by clozapine in the occurrence of chromosomal abnormalities.

Long-term of phenytoin: Effects on whole blood and red cell folate and haematological parameters.

Patients treated when phenytoin for periods of several months or years have slightly, but significantly lower whole blood and red cell folate values than comparable controls. This holds true irrespective of whether folate is determined microbiologically with Lactobacillus casei or by a radioligand method using the bovine milk binder. Haematological parameters including Hb, MCH, MCV and red blood cell counts did not show any alterations and no patient developed any signs of anaemia. This indicates that long-term use of phenytoin does not cause a clinically significant state of folate deficiency, unless some other contributing factors are present.