Chenodeoxycholic acid supplementation in an infant with cerebrotendinous xanthomatosis

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A two-week old girl was started on chenodeoxycholic acid (CDCA) supplementation, which inhibits cholestanol production through a feedback mechanism, at the advised dosage of 15 mg/kg/day. Within 6 weeks, she developed jaundice with hepatomegaly. CDCA supplementation was stopped after which liver size and function rapidly normalised. CDCA supplementation was then restarted andmaintained at 5 mg/kg/day. Cholestanol, liver enzymes and total bilirubin were frequently monitored in the patient, who is now 2.8 years of age, and have remained within normal range. Her psychomotor development has been normal.
This results in a reduced production of chenodeoxycholic acid (CDCA) and cholic acid (CA) and accumulation of cholestanol and cholesterol in different tissues. Clinical features of CTX include neonatal cholestasis, bilateral cataract and chronic diarrhoea during childhood and tendon xanthomas and various neuropsychiatric symptoms, including pyramidal and cerebellar signs, peripheral neuropathy and dementia, from the second decade onward. The development of these symptoms can be halted or prevented by supplementation of Chenodeoxycholic acid, which reduces bile acid synthesis via direct inhibition of the enzyme cholesterol-7α-hydroxylase (CYP7A1) and via negative feedback on cholesterol biosynthesis. The prognosis of CTX is good when therapy is started early but is less favourable when initiated at a later age. Because early detection and start of treatment likely prevents symptoms, CTX is a good candidate for newborn screening. Although a validated screening method is not yet available, DeBarber et al. recently published a potential screening method for CTX based on the quantification of ketosterols.
The advised dosage of Chenodeoxycholic acid(CDCA) supplementation in children with CTX is 15 mg/kg/day. Here, we describe an infant with CTX who developed toxic hepatitis with CDCA supplementation at this dosage and demonstrate that adequate metabolic control in infants and young children with CTX can also be achieved with the lower dosage of 5 mg/kg/day of CDCA. This is relevant in view of the possible inclusion of CTX in newborn screening programs in the near future. A girl, the second child of Dutch, non-consanguineous parents, was born at term after an uneventful pregnancy and delivery with a normal birth weight and normal Apgar scores. At day 8, she presented with feeding difficulties, lethargy and temperature instability, followed by convulsions for which continuous midazolam was started.