Bile acid CoA ligase deficiency and defective amidation

Bile acid CoA ligase deficiency and defective amidation is an extremely rare inborn error of bile acid metabolism caused by mutations in the SLC27A5 gene (also known as BACS or VLCS-H2), which encodes the bile acid CoA ligase (also called very long-chain acyl-CoA synthetase). This enzyme is essential for the conjugation (amidation) of primary bile acids with the amino acids glycine and taurine in the liver. When this enzyme is deficient, unconjugated and atypical bile acids accumulate, leading to impaired bile acid function and hepatotoxicity. The condition primarily affects the hepatobiliary system. Patients typically present in infancy or early childhood with features of cholestatic liver disease, including jaundice, hepatomegaly, elevated serum bile acids, and fat-soluble vitamin malabsorption. Liver biopsy may show giant cell hepatitis or progressive fibrosis. Without treatment, the disease can progress to cirrhosis and liver failure. Laboratory findings characteristically show the presence of unconjugated bile acids and reduced or absent conjugated bile acid species in bile and serum. Treatment involves oral bile acid replacement therapy, typically with cholic acid or ursodeoxycholic acid, which can suppress the production of toxic atypical bile acids through negative feedback on bile acid synthesis. Early diagnosis and initiation of bile acid therapy are critical to prevent irreversible liver damage. In severe or advanced cases, liver transplantation may be considered. The condition is inherited in an autosomal recessive manner, and genetic testing of SLC27A5 can confirm the diagnosis.

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