Chronic diarrhea and juvenile cataracts: think cerebrotendinous xanthomatosis and treat

Cerebrotendinous xanthomatosis is an autosomal recessive disease of bile acid synthesis caused by 27-hydroxylase deficiency. Treatment with chenodeoxycholic acid normalizes cholestanol concentrations and abrogates progression of the disease. We present 4 patients with cerebrotendinous xanthomatosis within 1 family who were treated with chenodeoxycholic acid for 14 years. Two young sisters started treatment at the preclinical stage before the appearance of major symptoms. Their 2 older uncles, who had already developed the complete phenotypic form of cerebrotendinous xanthomatosis when diagnosed, commenced treatment at the same time as the sisters, thus establishing a natural control group. After 14 years of chenodeoxycholic acid therapy, the cholestanol levels of all 4 patients decreased to normal levels (<6 microg/mL). Both sisters remained asymptomatic. Only moderate improvement in symptoms was observed in their uncles. In this long-term study, prompt preclinical administration of chenodeoxycholic acid in early childhood completely prevented the cerebrotendinous xanthomatosis phenotype in 2 sisters. Pediatricians should be aware of this diagnostic possibility of cerebrotendinous xanthomatosis in children presenting with chronic diarrhea and juvenile cataracts. Prevention is particularly significant in light of the availability of early genetic diagnosis and the devastating effects of this illness if not treated.