Cerebrotendinous xanthomatosis in Slovak patients - experience with clinical manifestations and diagnostic approaches.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis caused by pathogenic variants in CYP27A1. The disease is characterized by progressive neurological impairment, cataracts, and tendon xanthomas and is biochemically defined by the accumulation of cholestanol, cholesterol precursors, and bile alcohols. We report the first Slovak cohort of eight CTX patients diagnosed using combined biochemical and molecular genetic approaches. Four adult patients were referred for laboratory investigation due to neurological manifestations, predominantly ataxia and spastic paraparesis, with diagnosis established in the fourth decade of life. Among the remaining individuals, two children and one adolescent were diagnosed based on cataracts or neurological symptoms, while one middle-aged woman was identified through family screening and presented mainly with psychiatric manifestations. All patients exhibited markedly elevated serum cholestanol concentrations, consistently accompanied by increased 7-dehydrocholesterol as a side finding. Molecular analysis identified six pathogenic variants (c.379 C > T, c.819delT, c.1016 C > T, c.1183 C > T, c.1184 + 1G > A, and c.1263 + 5G > A), including the intronic variant c.1263 + 5G > A, which has not been previously reported in CTX patients. The clinical manifestations observed in this cohort illustrate the broad phenotypic variability of CTX and reflect diagnostic process leading to disease recognition. Increased awareness of these clinical manifestations may prompt earlier laboratory evaluation using biochemical and molecular genetic testing.