Abnormal bile acid metabolism and neonatal hemochromatosis: a subset with poor prognosis.
BACKGROUND
Inborn errors of bile acid synthesis are newly recognized disorders that may cause the phenotypic appearance of neonatal hepatitis or neonatal cholestasis.


METHODS
This is a clinicopathologic study of two sets of siblings with cholestatic neonatal liver failure.


RESULTS
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 deficiency, which could be primary or secondary. The fourth infant died before such testing could be carried out. In addition, all 4 infants had histologically disseminated hemochromatosis and met diagnostic criteria for neonatal hemochromatosis. In the 3 infants studied, histologic examination of the liver disclosed giant cell hepatitis with extensive loss of hepatic parenchyma and rapid progression to cirrhosis. Early treatment with ursodeoxycholic acid and cholic acid, previously reported as effective therapy, was given to 2 siblings; it failed to reverse or halt the liver damage, and both infants died. One infant, with the original diagnosis of neonatal hemochromatosis, was treated with a variety of antioxidants and chelation therapy, as recently reported. No improvement was demonstrated, and he went on to liver transplantation.


CONCLUSIONS
The presentation of delta 4-3-oxosteroid 5 beta-reductase deficiency as neonatal hemochromatosis may represent a distinct subset of this disorder with an accelerated course, no response to therapy and poor prognosis.
Siafakas
C G
CG
Department of Medicine, Children's Hospital, Boston, MA 02118, USA.
Jonas
M M
MM
Perez-Atayde
A R
AR
D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000209:etiology / Q000473:pathology / Q000628:therapy; D019826:Cholic Acid; D002793:Cholic Acids / Q000627:therapeutic use; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006432:Hemochromatosis / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000209:etiology / Q000473:pathology / Q000628:therapy; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D010088:Oxidoreductases / Q000172:deficiency*; D011379:Prognosis; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D001647:Bile Acids and Salts; D002793:Cholic Acids; D014580:Ursodeoxycholic Acid; D010088:Oxidoreductases; C051860:cholestenone 5 beta-reductase; D019826:Cholic Acid