Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes.

Objectives: HSD3B7 deficiency is a genetic disorder caused by mutations in the gene, leading to impaired bile acid synthesis and the accumulation of toxic intermediates. Affected patients typically present with cholestatic liver disease, including jaundice and progressive liver dysfunction.

Case Presentation: This case series describes three pediatric patients from two families diagnosed with HSD3B7 deficiency, each demonstrating varying clinical severity and outcomes. All cases exhibited cholestasis with normal GGT levels and elevated AST/ALT. Case 1, a male infant, also presented with craniosynostosis and failure to thrive, responding well to cholic acid therapy. Case 2, a female infant and first cousin of Case 1, had mild cardiac abnormalities and showed slight improvement with ursodeoxycholic acid and vitamin supplementation. Case 3, a male infant with a compound and mutation, progressed to fulminant liver failure, ultimately requiring a liver transplant. A novel c.531 + 1G>C variant was identified in Cases 1 and 2, contributing to understanding genotype-phenotype correlations in bile acid synthesis disorders.

Conclusions: Early diagnosis and treatment with bile acid therapy are crucial for improving outcomes, although some cases may necessitate liver transplantation. This series emphasizes the need to consider bile acid synthesis disorders in the differential diagnosis of cholestasis.