Inborn errors of bile acid metabolism in Japan

Bile acids are a category of steroids biosynthesized from cholesterol in the liver. Inborn errors of their metabolism are inherited in an autosomal recessive manner, resulting in enzyme deficiencies affecting the bile acid biosynthetic pathway. These defects in the pathway cause accumulation of unusual bile acids or bile alcohols. Unusual bile acids are highly cytotoxic, causing injury to the liver. These unusual bile acids damage hepatocytes, resulting in cholestatic liver injury beginning in infancy. Except for cerebrotendinous xanthomatosis and some secondary defects, various inborn errors of bile acid metabolism (IEBAM) have been reported from Japan, affecting eight patients including three with 3 beta-hydroxy-Delta(5)-C-27-steroid dehydrogenase/isomerase deficiency, three with Delta(4)-3-oxosteroid 5 beta-reductase deficiency, one with oxysterol 7 alpha-hydroxylase deficiency, and one with bile acid-CoA: amino acid N-acyltransferase deficiency. Distinctive laboratory findings in patients with 3 beta-hydroxy-Delta(5)-C-27-steroid dehydrogenase/isomerase deficiency, Delta(4)-3-oxosteroid 5 beta-reductase deficiency, and oxysterol 7 alpha-hydroxylase deficiency include normal serum gamma-glutamyltransferase and total bile acids concentrations despite presence of cholestasis (elevated serum direct bilirubin) from infancy. Pediatricians and pediatric surgeons who suspect a case of IEBAM should obtain urinary and serum bile acid analyses using gas or liquid chromatography--mass spectrometry as well as genetic analyses. Available treatments include oral cholic acid, chenodeoxycholic acid, glycocholic acid, and ursodeoxycholic acid; fat-soluble vitamin supplementation; and liver transplantation. Early diagnosis and treatment can offer a good outcome.