ABNORMAL BILE-ACID METABOLISM AND NEONATAL HEMOCHROMATOSIS - A SUBSETWITH POOR-PROGNOSIS

Background: Inborn errors of bile acid synthesis are newly recognized disorders that may cause the phenotypic appearance of neonatal hepatit is or neonatal cholestasis. Methods: This is a clinicopathologic study of two sets of siblings with cholestatic neonatal liver failure. Resu lts: In 3 of the infants, diagnostic evaluation. including analysis of urinary bile salts, revealed a predominance of 7 alpha-hydroxy-3-oxo- 4-cholenoic and 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acids, a pattern consistent with Delta(4)-3-oxosteroid 5 beta-reductase defici ency, which could be primary or secondary. The fourth infant died befo re such testing could be carried out. In addition, all 4 infants had h istologically disseminated hemochromatosis and met diagnostic criteria for neonatal hemochromatosis. In the 3 infants studied, histologic ex amination of the liver disclosed giant cell hepatitis with extensive l oss of hepatic parenchyma and rapid progression to cirrhosis. Early tr eatment with ursodeoxycholic acid and cholic acid, previously reported as effective therapy, was given to 2 siblings; it failed to reverse o r halt the liver damage, and both infants died. One infant, with the o riginal diagnosis of neonatal hemochromatosis, was treated with a vari ety of antioxidants and chelation therapy, as recently reported. No im provement was demonstrated, and he went on to liver transplantation. C onclusions: The presentation of Delta(4)-3-oxosteroid 5 beta-reductase deficiency as neonatal hemochromatosis may represent a distinct subse t of this disorder with an accelerated course, no response to therapy and poor prognosis.(C) 1997 Lippincott-Raven Publishers.