Congenital bile acid synthesis defect type 4

Congenital bile acid synthesis defect type 4 (CBAS4), also known as amidation defect of bile acid synthesis or bile acid-CoA:amino acid N-acyltransferase (BAAT) deficiency, is a rare inherited disorder of bile acid metabolism caused by mutations in the BAAT gene. This enzyme is responsible for the final step in bile acid synthesis, specifically the conjugation (amidation) of bile acids with the amino acids glycine or taurine. Without proper conjugation, bile acids cannot be efficiently secreted into bile, leading to impaired bile flow and accumulation of unconjugated bile acids. The disease primarily affects the liver and gastrointestinal system. Patients typically present in infancy or early childhood with cholestatic liver disease, which may include jaundice, pruritus (itching), hepatomegaly (enlarged liver), fat-soluble vitamin malabsorption, steatorrhea (fatty stools), and failure to thrive. If untreated, progressive liver damage can occur, potentially leading to fibrosis and cirrhosis. Laboratory findings often include elevated serum bile acids, conjugated hyperbilirubinemia, and elevated liver transaminases. Treatment involves oral bile acid replacement therapy, typically with glycocholic acid or other conjugated bile acids, which can help restore normal bile flow and reduce the accumulation of toxic unconjugated bile acid intermediates. Ursodeoxycholic acid (UDCA) has also been used in some patients. Fat-soluble vitamin supplementation (vitamins A, D, E, and K) is important to address malabsorption. Early diagnosis and treatment can significantly improve outcomes and may prevent progressive liver disease. In severe or refractory cases, liver transplantation may be considered.

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