Case Report: Primary bile acid synthesis defect: first cases series from Tunisia

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.

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.

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 3β-hydroxysteroid dehydrogenase deficiency, including three siblings homozygous for a novel HSD3B7 variant (c.748_760del) and their brother, who remained genetically undiagnosed despite extensive investigation. One patient had Δ⁴-3-oxosteroid 5β-reductase (5β-R) deficiency carrying a known AKR1D1 variant (c.242A>T). Three patients received CA therapy (6.2-13.4 mg/kg/day), achieving complete clinical and biochemical remission during 5-6 years of follow-up. Conversely, three patients died from liver failure before CA treatment could be initiated.

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.