Presence of diarrhea and absence of tendon xanthomas in patients with cerebrotendinous xanthomatosis.

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis. A diagnosis of CTX should be considered in patients with premature bilateral cataracts, intractable diarrhea, neurological signs and symptoms, and tendon xanthomas, especially in the Achilles tendons. The prevalence of these signs and symptoms increases with age.

Objectives: To investigate signs and symptoms, age at onset, and age at diagnosis in 32 patients with biochemically and genetically confirmed CTX, and to compare this clinical spectrum with reports in the literature.

Methods: Retrospective analysis of records of all patients with CTX at our hospital (27 adults and 5 children). After a MEDLINE search in the English, French, and German literature, 181 patients with CTX (165 adults and 16 children) were identified worldwide.

Results: Of our 32 patients with CTX, 31 (97%) had cataracts and neurological signs and symptoms, predominantly pyramidal signs (26 [81%]); 21 (66%) had low intelligence and 18 (56%) had cerebellar signs. Only 13 (41%) had visible or palpable tendon xanthomas at the time of diagnosis. In total, 16 patients (50%) had chronic, intractable diarrhea that started in childhood. These findings were in contrast with the literature, where tendon xanthomas were reported in 89% and diarrhea in only 2 patients.

Conclusions: We believe that CTX is underdiagnosed worldwide. We recommend that the presence of 2 of the 4 clinical hallmarks of CTX prompt thorough metabolic screening, including determination of urine bile alcohol excretion and serum cholestanol level, because CTX is a treatable disease.