Inborn errors of bile acid metabolism.

Bile acids are synthesized by the liver from cholesterol through a complex series of reactions involving at least 14 enzymatic steps. A failure to perform any of these reactions will block bile acid production with failure to produce "normal bile acids" and, instead, result in the accumulation of unusual bile acids and intermediary metabolites. Failure to synthesize bile acids leads to reduced bile flow and decreased intraluminal solubilization of fat and fat-soluble vitamins. In some circumstances, the intermediates created because of blockade in the bile acid biosynthetic pathway may be toxic to hepatocytes. Nine recognized inborn errors of bile acid metabolism have been identified that lead to enzyme deficiencies and impaired bile acid synthesis in infants, children, and adults. Patients may present with neonatal cholestasis, neurologic disease, or fat and fat-soluble vitamin malabsorption. If untreated, progressive liver disease may develop or reduced intestinal bile acid concentrations may lead to serious morbidity or mortality. This review focuses on a description of the disorders of bile acid synthesis that are directly related to single defects in the metabolic pathway, their proposed pathogenesis, treatment, and prognosis.