Case Report: Early Treatment With Chenodeoxycholic Acid in Cerebrotendinous Xanthomatosis Presenting as Neonatal Cholestasis

Abstract

Background: Cerebrotendinous xanthomatosis (CTX) is an inborn disorder of bile acid synthesis which causes progressive accumulation of toxic metabolites in various organs, particularly in brain and tendons. Most cases are diagnosed and treated in the second or third decade of life, when neurological involvement appears. We describe a case of CTX presenting as neonatal cholestasis. Results: The child presented cholestasis at 2 months of life. In the following months jaundice slowly disappeared, with a normalization of bilirubin and aminotransferases, respectively, at 6 and 8 months. A LC-Mass Spectrometry of the urines showed the presence of cholestanepentols glucuronide, which led to the suspicion of cerebrotendinous xanthomatosis. The diagnosis was confirmed by the dosage of cholestanol in serum and the molecular genetic analysis of the CYP27A1 gene. Therapy with chenodeoxycholic acid (CDCA) was started at 8 months and is still ongoing. The child was monitored for 13 years by dosage of serum cholestanol and urinary cholestanepentols. A strictly biochemical and neurological follow up was performed and no sign of neurological impairment was observed. Conclusions: Prompt diagnosis and treatment of CTX presenting as neonatal cholestasis may prevent further neurological impairment.

Sterol 27-Hydroxylase Deficiency as a Cause of Neonatal Cholestasis: Report of 2 Cases and Review of the Literature

“…Degrassi et al have recently reported a patient who started to be treated at 8 months of age with the initial dose of 10 mg/kg/day, increased until 15 mg/kg/day. The patient has been followed for 13 years and the therapy was well-tolerated ( 18 ).…”

“…The retrospective analysis of the past medical records of 50 Dutch patients with CTX, authored by Clayton et al, revealed that neonatal liver disease defined as prolonged jaundice with raised serum transaminases occurred much more often in CTX than in the general population (13). Up to now, neonatal cholestatic jaundice in the course of CTX has been reported in 14 patients, in most of them presenting as a selflimiting disease (11)(12)(13)(14)(15)(16)(17)(18)(19). However, a fatal neonatal cholestasis has been reported in 5 out of 12 patients (Table 3).…”

“…Fourteen patients with sterol 27-hydroxylase deficiency presenting with neonatal cholestasis were reported, see Table 3 (11)(12)(13)(14)(15)(16)(17)(18)(19). To be noted that a detailed clinical presentation was not available in some of the reported cases (12,14,17,19).…”

First case series of Polish patients with cerebrotendinous xanthomatosis and systematic review of cases from the 21st century

“…Chenodeoxycholic acid is the current standard of therapy. 35 With treatment started early, the improvement in patients can be remarkable. 35,202 Unfortunately, treatment initiated too late can bring no favorable effects.…”

Gene supplementation of CYP27A1 in the liver restores bile acid metabolism in a mouse model of cerebrotendinous xanthomatosis

“…4 CTX patients present complex and heteroge-neous clinical manifestations, including chronic diarrhea with infantile onset, juvenile cataracts, tendon xanthomas, osteoporosis, premature atherosclerosis, mild respiratory insufficiency, and progressive neuropsychiatric alterations (ataxia, peripheral neuropathy, epilepsy, depression, and cognitive deterioration). 5 Some reports describe cases of severe infantile cholestasis, [6][7][8] although liver damage is not a common characteristic of this disease. The onset and severity of symptoms differ among CTX patients, which contributes to the fact that their diagnosis is usually delayed more than 15 years.…”