Mechanisms of disease: Inborn errors of bile acid synthesis.

[zellweger syndrome]

Inborn errors of bile acid synthesis are rare genetic disorders that can present as neonatal cholestasis , neurologic disease or fat-soluble-vitamin deficiencies . There are nine known defects of bile acid synthesis , including oxysterol 7 alpha-hydroxylase deficiency , Delta (4 )-3 -oxosteroid-5 beta -reductase deficiency , 3 beta -hydroxy-Delta (5 )-C (27 )-steroid dehydrogenase deficiency , cerebrotendinous xanthomatosis (also known as sterol 27 -hydroxylase deficiency ), alpha-methylacyl-CoA racemase deficiency , and Zellweger syndrome (also known as cerebrohepatorenal syndrome ). These diseases are characterized by a failure to produce normal bile acids and an accumulation of unusual bile acids and bile acid intermediaries . Individuals with inborn errors of bile acid synthesis generally present with the hallmark features of normal or low serum bile acid concentrations , normal gamma-glutamyl transpeptidase concentrations and the absence of pruritus . Failure to diagnose any of these conditions can result in liver failure or progressive chronic liver disease . If recognized early , many patients can have a remarkable clinical response to oral bile acid therapy .