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Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis
B L Shneider1, K D Setchell, P F Whitington
1Yale University, Department of Pediatrics, New Haven, CT 06520.
Insights
Two infants with neonatal liver failure and hemochromatosis were diagnosed with a rare bile acid synthesis defect, delta 4-3-oxosteroid 5 beta-reductase deficiency. This genetic disorder impacts bile acid production and iron metabolism.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Medicine
Background:
- Neonatal liver failure is a critical condition with diverse etiologies.
- Bile acid synthesis defects are rare genetic disorders affecting liver function.
- Hemochromatosis, or iron overload, can be associated with various conditions.
Abstract:
Neonatal liver failure was evaluated in two infants. Neither infant had evidence of congenital infection, galactosemia, alpha 1-antitrypsin deficiency, tyrosinemia, Zellweger syndrome, or hemophagocytic lymphohistiocytosis. Abnormal levels of iron were detected in the minor salivary glands of the first infant and in the explanted liver of the second. Analyses of urinary bile salts by fast-atom bombardment ionization mass spectrometry and gas chromatography-mass spectrometry revealed a paucity of primary bile acids and a predominance of 7 alpha-hydroxy-3-oxo-4-cholenoic and 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acids. These findings are consistent with delta 4-3-oxosteroid 5 beta-reductase deficiency, a primary genetic defect in bile acid synthesis. Postmortem evaluation of the first infant revealed significant iron deposition in the liver, pancreas, thyroid, adrenal glands, myocardium, stomach, and submucosal glands of the respiratory tract. In both infants examination of the liver revealed extensive loss of hepatic parenchyma. These cases expand the clinical spectrum of bile acid metabolism defects to include neonatal liver failure with associated hemochromatosis.