4-3-oxo-5-reductase deficiency: favorable outcome in 16 patients treated with cholic acid
ORPHANET JOURNAL OF RARE DISEASES(2023)
摘要
Background: Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3 beta-hydroxy-Delta(5)-C-27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Delta(4)-3-oxosteroid 5 beta-reductase (Delta(4)-3-oxo-R) deficiency.Methods: Sixteen patients with Delta(4)-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed.Results: First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1-159) and serum liver tests normalized in all within 6-12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1-24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-triangle(4) derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity.Conclusions: Oral cholic acid therapy is a safe and effective treatment for patients with Delta(4)-3-oxo-R deficiency.
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关键词
Bile acid,Genetic cholestasis
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