Prospective treatment of cerebrotendinous xanthomatosis with cholic acid therapy

Abstract

Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare disorder of bile acid synthesis caused by deficiency of the enzyme sterol 27-hydroxylase. It results in deficiency of bile acids and accumulation of abnormal bile alcohols and accelerated cholesterol synthesis. CTX usually presents in the second or third decade with slowly progressive neurological dysfunction, cerebellar ataxia and premature atherosclerosis. Treatment with bile acid supplementation improves but does not completely reverse the neurological signs and symptoms. However, CTX is now known to be associated with a period of neonatal cholestasis. If it is diagnosed at this point, treatment may prevent the onset of neurological problems. We present the case histories and developmental findings in two affected siblings treated from infancy. We plan to continue regular neurodevelopmental reviews.

Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis

“…In 2015, cholic acid was approved for the treatment of bile acid synthesis disorders due to single-enzyme defects, including CTX, based on data from several pediatric cases. [30][31][32] This approval was granted even though experience with this therapy was extremely limited and there were no long-term safety or efficacy data. The first case treated was the male offspring of consanguineous Asian parents.…”

“…The first case treated was the male offspring of consanguineous Asian parents. 30 He developed unexplained neonatal jaundice shortly after birth, and was found to have elevated liver transaminases, bilirubin, and alkaline phosphatase. A liver biopsy showed chronic active hepatitis with necrosis and moderate fibrosis.…”

A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns

“…CDCA treatment has been shown to normalize the biochemical phenotype and halt progression of disease ( 10,12 ). There are reports indicating treatment prevents the onset of disease complications in presymptomatic children ( 13,14 ). Cholic acid treatment has been reported to be a less hepatotoxic alternative to CDCA in infants ( 13 ).…”

“…There are reports indicating treatment prevents the onset of disease complications in presymptomatic children ( 13,14 ). Cholic acid treatment has been reported to be a less hepatotoxic alternative to CDCA in infants ( 13 ). Although treatment at every stage of disease is recommended ( 15 ), in many cases, treatment of patients with advanced neurological disease does not reverse the neurological impairment ( 10 ).…”

Children with cataract and chronic diarrhoea: Cerebrotendinous xanthomatosis

“…Pierre and co-workers (Pierre et al, 2008)i n c o r r e c t l y cited the article of Kuriyama and co-workers (Kuriyama et al 1991)a sr e f e r e n c ef o rt h ep r e s e n t a t i o no f cerebrotendinous xanthomatosis in childhood with chronic diarrhoea. However, Kuriyama_s article does not report chronic diarrhoea at all.…”