Primary bile acid synthesis disorders

Primary bile acid synthesis disorders (BASDs) are rare autosomal recessive diseases characterized by multisystem manifestations, including cholestasis, progressive liver damage, and impaired absorption of fat-soluble vitamins. Diagnosis is challenging due to nonspecific clinical features, requiring a comprehensive approach that includes biochemical analysis, mass spectrometry, and genetic testing. Objective. To review current data on the pathogenesis, clinical manifestations, diagnosis, and treatment approaches for primary disorders of BASDs, including deficiencies of key enzymes involved in their metabolism. Key points. BASDs synthesis is regulated by a complex enzymatic system, where mutations lead to the accumulation of toxic intermediate metabolites. Key clinical signs include cholestasis, absence of pruritus, normal gamma-glutamyl transpeptidase levels, and low serum bile acids concentrations. Modern diagnostic methods include next-generation sequencing (NGS), tandem mass spectrometry, and liver histology. Bile acid replacement therapy is the primary treatment, while liver transplantation is considered in severe cases. Conclusion. Early diagnosis of primary BASDs is crucial for improving patient outcomes. Advances in molecular technologies facilitate the identification of rare mutations and the development of personalized treatment strategies.