Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized

Background Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurodegenerative disorder caused by 27-sterol hydroxylase (CYP27) deficiency. Objective To describe clinical features and results of genetic analysis in a family with CTX. Design Case report. Setting University hospital. Subjects A 54-year-old woman with CTX, her family members, and 115 white control subjects. Main Outcome Measures Results of clinical evaluation and magnetic resonance imaging of the brain in the affected subject; results of mutation analysis of the CYP27 coding sequence in the patient, her parents, and the control subjects. Results The proband and her affected sibling had classic features of CTX, including presenile cataracts, tendon xanthomas, diarrhea, and a complex neurodegenerative disorder. They were somewhat atypical, however, because their cataracts were congenital, cognitive impairment had been noted in childhood, and the white matter involvement was more severe than usual. The proband was shown to be homozygous for CYP27 mutation R362C. Similar analysis of 115 control subjects identified 1 subject who was a heterozygous carrier for this same CYP27 mutation. Conclusions The prevalence of CTX due to CYP27 mutation R362C alone is approximately 1 per 50 000 among white individuals. Although the disorder is rare, this incidence is substantially greater than previously recognized. Greater awareness of CTX is important because specific treatment is available.