Significance of Genetic Testing in Diagnosing Cholestatic Disease in Infants

基因检测在诊断婴儿胆汁淤积性疾病中的意义

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Abstract

Congenital bile acid synthesis defect type 1 (CBASD1) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the HSD3B7 gene, resulting in defective bile acid synthesis and accumulation of hepatotoxic intermediates. We report a seven-month-old female infant born to consanguineous parents who presented with progressive jaundice since one month of age, severe pruritus, failure to thrive, and abdominal distension with hepatosplenomegaly. Biochemical evaluation revealed marked conjugated hyperbilirubinemia, elevated cholestatic enzymes, coagulopathy, and mild hypoalbuminemia, with low-normal gamma-glutamyl transferase levels. Elastography demonstrated advanced fibrosis (F4), and abdominal computed tomography showed cirrhotic liver changes with splenomegaly. Due to progressive liver failure despite medical therapy, the patient underwent living donor liver transplantation. The explanted liver demonstrated cholestatic hepatitis and cirrhosis, with ductular proliferation and giant-cell transformation, and no evidence of malignancy. Subsequent genetic testing identified a homozygous pathogenic mutation in the HSD3B7 gene, confirming the diagnosis of CBASD1. This case highlights the importance of early biochemical evaluation, urine bile acid profiling, and genetic testing in infants with low gamma-glutamyl transferase (GGT) cholestasis to enable timely diagnosis, continue medical optimization, and proceed with liver transplant in the future.

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