{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:09:00Z","timestamp":1788952140395,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary bile acid synthesis defects (BASD) are autosomal recessive disorders causing cholestatic liver disease and fat-soluble vitamin malabsorption. Despite being treatable with cholic acid (CA), BASD remain underdiagnosed, particularly in resource-limited settings. No data have been published from Tunisia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective study of all patients diagnosed with BASD at La Rabta University Hospital in Tunis, between 2013 and 2024 described clinical presentation, biochemical and genetic findings, treatment and outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six male patients from three unrelated families were enrolled. The age at symptom onset ranged from the neonatal period to 8 years, with a diagnostic delay spanning from 1.5 months to 5 years. Three distinct phenotypes were observed: cholestasis (3\/6), malabsorption (4\/6), and non-cholestatic hepatopathy (1\/6). Four patients presented with 3\u03b2-hydroxysteroid dehydrogenase deficiency, including three siblings homozygous for a novel\n                      <jats:italic>HSD3B7<\/jats:italic>\n                      variant (c.748_760del) and their brother, who remained genetically undiagnosed despite extensive investigation. One patient had \u0394\n                      <jats:sup>4<\/jats:sup>\n                      -3-oxosteroid 5\u03b2-reductase (5\u03b2-R) deficiency carrying a known\n                      <jats:italic>AKR1D1<\/jats:italic>\n                      variant (c.242A&amp;gt;T). Three patients received CA therapy (6.2\u201313.4\u2005mg\/kg\/day), achieving complete clinical and biochemical remission during 5\u20136 years of follow-up. Conversely, three patients died from liver failure before CA treatment could be initiated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This first Tunisian small series highlights the phenotypic heterogeneity of BASD, even in the same family, and the efficacy of CA therapy when initiated early. Besides low GGT cholestasis, fat-soluble vitamin malabsorption and non-cholestatic liver phenotype require investigation of serum bile acids as well as bile acids in urine. Improved access to specialized diagnostic tools and orphan drug therapies is urgently needed in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1895852","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:12:15Z","timestamp":1788948735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Primary bile acid synthesis defect: first cases series from Tunisia"],"prefix":"10.3389","volume":"14","author":[{"given":"Mouna","family":"Zribi","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Metabolic Diseases, La Rabta University Hospital","place":["Tunis, Tunisia"]},{"name":"Faculty of Medicine of Tunis, University of Tunis El Manar","place":["Tunis, Tunisia"]},{"name":"Research Laboratory LR12SP02 \u201cInherited Metabolic Diseases: Investigation and Management\u201d, La Rabta University Hospital","place":["Tunis, Tunisia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Khatrouch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Metabolic Diseases, La Rabta University Hospital","place":["Tunis, Tunisia"]},{"name":"Faculty of Medicine of Tunis, University of Tunis El Manar","place":["Tunis, Tunisia"]},{"name":"Research Laboratory LR12SP02 \u201cInherited Metabolic Diseases: Investigation and Management\u201d, La Rabta University Hospital","place":["Tunis, Tunisia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hela","family":"Boudabous","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Metabolic Diseases, La Rabta University Hospital","place":["Tunis, Tunisia"]},{"name":"Faculty of Medicine of Tunis, University of Tunis El Manar","place":["Tunis, Tunisia"]},{"name":"Research Laboratory LR12SP02 \u201cInherited Metabolic Diseases: Investigation and Management\u201d, 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