Cerebrotendinous xanthomatosis: molecular diagnosis enables presymptomatic detection of a treatable disease.

We report an early molecular diagnosis of cerebrotendinous xanthomatosis (CTX) in a Jewish Moroccan family with two affected siblings. The proband displayed characteristic manifestations of the disease, whereas a younger brother, homozygous for the mutant allele, was asymptomatic. Clinical studies in the younger patient disclosed mild cognitive impairment, peripheral neuropathy, and abnormal EEG. Elevated plasma cholestanol levels were evident in both affected patients, with documented normal levels in the molecularly diagnosed heterozygous family members. Molecular characterization of affected CTX families provides early diagnosis and treatment of homozygotes in the presymptomatic state as well as identification of heterozygotes, which is crucial for genetic counseling and for prenatal diagnosis.