Cg. Siafakas et al., ABNORMAL BILE-ACID METABOLISM AND NEONATAL HEMOCHROMATOSIS - A SUBSETWITH POOR-PROGNOSIS, Journal of pediatric gastroenterology and nutrition, 25(3), 1997, pp. 321-326
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.