학술논문
4-3-oxo-5[beta]-reductase deficiency: favorable outcome in 16 patients treated with cholic acid
Document Type
Academic Journal
Author
Gardin, Antoine; Ruiz, Mathias; Beime, Jan; Cananzi, Mara; Rathert, Margarete; Rohmer, Barbara; Grabhorn, Enke; Almes, Marion; Logarajah, Veena; Peéa-Quintana, Luis; Casswall, Thomas; Darmellah-Remil, Amaria; Reyes-Domínguez, Ana; Barkaoui, Emna; Hierro, Loreto; Baquero-Montoya, Carolina; Baumann, Ulrich; Fischler, Björn; Gonzales, Emmanuel; Davit-Spraul, Anne; Laplanche, Sophie; Jacquemin, Emmanuel
Source
Orphanet Journal of Rare Diseases. December 7, 2023, Vol. 18 Issue 1
Subject
Language
English
ISSN
1750-1172
Abstract
Author(s): Antoine Gardin[sup.1], Mathias Ruiz[sup.2], Jan Beime[sup.3], Mara Cananzi[sup.4], Margarete Rathert[sup.5], Barbara Rohmer[sup.2], Enke Grabhorn[sup.3], Marion Almes[sup.1], Veena Logarajah[sup.6], Luis Peéa-Quintana[sup.7], Thomas Casswall[sup.8], Amaria Darmellah-Remil[sup.1], Ana Reyes-Domínguez[sup.7], Emna Barkaoui[sup.9], Loreto [...]
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-[DELA].sup.5-C.sub.27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer [DELA].sup.4-3-oxosteroid 5[beta]-reductase ([DELA].sup.4-3-oxo-R) deficiency. Methods Sixteen patients with [DELA].sup.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-[DELA].sup.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 [DELA].sup.4-3-oxo-R deficiency. Keywords: Bile acid, Genetic cholestasis, AKR1D1
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-[DELA].sup.5-C.sub.27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer [DELA].sup.4-3-oxosteroid 5[beta]-reductase ([DELA].sup.4-3-oxo-R) deficiency. Methods Sixteen patients with [DELA].sup.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-[DELA].sup.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 [DELA].sup.4-3-oxo-R deficiency. Keywords: Bile acid, Genetic cholestasis, AKR1D1