Infantile cholestasis and secondary coagulopathy mimicking hemophilia B in a consanguineous family: Syria’s first documented case of HSD3B7 deficiency

Congenital Bile Acid Synthesis Defect Type 1 (CBAS1) is a rare autosomal recessive disorder caused by HSD3B7 variants. Its nonspecific presentation often delays diagnosis. We report the first genetically confirmed case from Syria, underscoring how clinical observation, biochemical markers, and family history can converge to establish a life‑saving diagnosis. A 5-year-old boy presenting with infantile cholestasis and severe secondary coagulopathy mimicking Hemophilia B, born to consanguineous parents, was first evaluated at 7 months for unexplained bruising. The initial coagulopathy was driven by profound vitamin K malabsorption secondary to cholestasis rather than primary intrinsic hepatocellular synthetic failure. By 10 months, he had developed features of chronic liver disease, including massive hepatosplenomegaly, esophageal varices, and early portal fibrosis. Despite persistent cholestasis, serum gamma-glutamyl transferase (GGT) activity remained normal. Genetic testing confirmed a homozygous HSD3B7 mutation. Initiation of ursodeoxycholic acid (UDCA) therapy at 15 mg/kg/day led to marked clinical improvement, with regression of hepatosplenomegaly, resolution of varices, and normalization of coagulation parameters without disease recurrence over a 4-year follow-up period. This case highlights the diagnostic value of normal GGT in the setting of cholestasis and secondary coagulopathy, particularly when combined with consanguinity and recurrent infantile liver disease in the family. Early recognition of this biochemical clue can prompt genetic testing and enable timely, targeted therapy. To our knowledge, this is the first genetically confirmed HSD3B7 deficiency reported from Syria.