{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:01:40Z","timestamp":1784682100447,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bile acid synthesis defects (BASDs) comprise a group of rare, often severe, metabolic disorders. Bile acid replacement therapy decreases toxic bile acid intermediates production and improves biochemical profiles, potentially delaying or stabilizing disease progression. An open label, non\u2010randomized trial with cholic acid (CA) supplementation included six patients with \u03b1\u2010methylacyl\u2010CoA racemase (AMACR) deficiency and one patient with 3\u03b2\u2010hydroxy\u2010\u0394\n                    <jats:sup>5<\/jats:sup>\n                    \u2010C\n                    <jats:sub>27<\/jats:sub>\n                    \u2010steroid oxidoreductase deficiency. Patients received up to 20\u2009mg\/kg\/day CA for 3.5\u2009years, adjusted for biochemical response, side effects, and clinical evaluation. Bile acid metabolites, liver enzymes, liver stiffness, and neurological symptoms were evaluated at baseline and during follow\u2010up. CA was well tolerated in children (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093), allowing for higher doses. Adults (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094) experienced more side effects, primarily diarrhea and other gastrointestinal symptoms. Children's transaminase levels normalized during treatment, while adults' levels remained normal throughout. Elevated C\n                    <jats:sub>27<\/jats:sub>\n                    \u2010bile acid intermediates, C\n                    <jats:sub>29<\/jats:sub>\n                    \u2010dicarboxylic acid, and pristanic acid were observed in all AMACR patients. C\n                    <jats:sub>27<\/jats:sub>\n                    \u2010bile acids and C\n                    <jats:sub>29<\/jats:sub>\n                    \u2010dicarboxylic acid decreased with treatment, while pristanic acid fluctuated and remained elevated. No clinically relevant changes were observed in liver elasticity, fat\u2010soluble vitamin levels, neurological assessment, or growth (in children). One adult developed hepatocellular carcinoma during treatment. CA treatment is generally safe, with acceptable tolerance and a marked biochemical response observed in children, although biomarker levels remained markedly elevated. In adults, however, the balance shifts negatively, with side effects outweighing the (biochemical) benefits. A longer study is necessary to evaluate the impact of CA treatment on the clinical relevance of the observed biochemical response.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70062","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:28:38Z","timestamp":1752236918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effectiveness and Safety of Personalized Cholic Acid Treatment in Patients With Bile Acid Synthesis Defects"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4730-354X","authenticated-orcid":false,"given":"Yasmin","family":"Polak","sequence":"first","affiliation":[{"name":"Platform Medicine for Society  Amsterdam the Netherlands"},{"name":"Department of Pharmacy and Clinical Pharmacology Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-1713","authenticated-orcid":false,"given":"Elles Marleen","family":"Kemper","sequence":"additional","affiliation":[{"name":"Platform Medicine for Society  Amsterdam the Netherlands"},{"name":"Department of Pharmacy and Clinical Pharmacology Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5346-8497","authenticated-orcid":false,"given":"Marc","family":"Engelen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-8837","authenticated-orcid":false,"given":"Femke C. C.","family":"Klouwer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Berendse","sequence":"additional","affiliation":[{"name":"The Pediatric Practice (de Kinderartsenpraktijk)  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-1041","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pediatrics Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4350-3084","authenticated-orcid":false,"given":"Bart G. P.","family":"Koot","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora (Noortje) L.","family":"Swart","sequence":"additional","affiliation":[{"name":"Platform Medicine for Society  Amsterdam the Netherlands"},{"name":"Department of Pharmacy and Clinical Pharmacology Amsterdam UMC, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-1078","authenticated-orcid":false,"given":"Carla E. 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