Chenodeoxycholic acid (CDCA) test on a two-week old girl

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Coincidently, the metabolic screening demonstrated an elevated plasma cholestanol (21.5 μmol/L; reference range (age 0–100 days) 2.8–19.0 μmol/L), a low Chenodeoxycholic acid (0.1 mmol/L; reference range 0.7–10.0 μmol/L) and CA (0.4 mmol/L; reference range 0.1–4.7 μmol/L) and urinary excretion of the characteristic glucuronic acid conjugates of bile alcohols (cholestanetetrol, pentol and hexol), consistent with the diagnosis of CTX. No other metabolic abnormalities were detected. Mutation analysis of CYP27A1 revealed two known missense mutations, c.1016C>T (p.Thr339Met) and c.1183C>T(p.Arg395Cys) confirming the diagnosis of CTX.
Viral hepatitis due to an Epstein-Barr virus or cytomegalovirus infection was excluded. Chenodeoxycholic acid supplementation was stopped to rule out toxic hepatitis. Plasma CDCA concentration at this time was 467 μmol/L. After cessation of CDCA supplementation, liver size normalised within 1 month and liver enzymes returned to normal values within 3 months. CDCA supplementation was restarted at a dosage of 5 mg/kg/day, resulting in the normalisation of plasma cholestanol (reference range (age>100 days) 3.5–10.0 μmol/L) and a plasma CDCA concentration between 6 and 12 μmol/L. The urinary excretion of CTX glucuronic acid conjugates of bile alcohols decreased to almost undetectable. The patient has been maintained on a Chenodeoxycholic acid dosage of 5 mg/kg/day since, and the plasma cholestanol concentration has remained within the normal range during 2.5 years of treatment. The patient’s growth and psychomotor development have been normal, and no clinical or neurological signs of CTX have been detected until now.
Plasma cholestanol,Chenodeoxycholic acid, ALT and total bilirubin concentrations before CDCA supplementation, during CDCA supplementation at 15 mg/kg/day and 5 mg/kg/day and in the period without treatment are shown. Cerebrotendinous xanthomatosis (CTX) is a well-established metabolic disorder of bile acid synthesis with serious progressive neurological sequelae without treatment. Supplementation of CDCA has been proven effective in mitigating the symptoms of CTX and will probably prevent the neurological phenotype when treatment is started at an early age. Therefore, CTX is a good candidate for implementation in newborn screening programs. Currently, screening methods are being developed to make this feasible, and it is expected that CTX will be included in newborn screening programs in the near future.