congenital defect in bile acid synthesis type 2

Synopsis

 neonatal cholestatic jaundice
 neonatal severe intrahepatic cholestasis
 neonatal liver failure (8301429)
 possible neonatal hemochromatosis (8301429)
 defective primary bile acid synthesis
 markedly increased levels of atypical oxo and allo bile acids in urine and serum
 severe neonatal cholestasis
 coagulopathy
 almost complete absence of chenodeoxycholic and cholic acids

Microscopy

 hepatocellular cholestasis
 giant-cell transformation of hepatocytes ("giant cell hepatitis")
 possible neonatal hemochromatosis (8301429)
 portal fibrosis

Etiology

 germline mutations in AKR1D1 (aldo-keto reductase family 1, member D1 (MIM.604741)

• Human delta(4)-3-oxosteroid 5-beta-reductase (steroid 5-beta-reductase; EC 1.3.1.23) catalyzes 5-beta-reduction of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure.

See also

 congenital defects in bile acid synthesis (CBASs)

• congenital defect in bile acid synthesis type 2 (CBAS2)

References

 Lemonde, H. A., Custard, E. J., Bouquet, J., Duran, M., Overmars, H., Scambler, P. J., Clayton, P. T. Mutations in SRD5B1 (AKR1D1), the gene encoding delta-4-3-oxosteroid 5-beta-reductase, in hepatitis and liver failure in infancy. Gut 52: 1494-1499, 2003. [PubMed: 12970144]

 Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis. Shneider BL, Setchell KD, Whitington PF, Neilson KA, Suchy FJ. J Pediatr. 1994 Feb;124(2):234-8. PMID: 8301429

 Setchell, K. D. R., Suchy, F. J., Welsh, M. B., Zimmer-Nechemias, L., Heubi, J., Balistreri, W. F. Delta(4)-3-oxosteroid 5-beta-reductase deficiency described in identical twins with neonatal hepatitis: a new inborn error in bile acid synthesis. J. Clin. Invest. 82: 2148-2157, 1988. [PubMed: 3198770]

 Shneider, B. L., Setchell, K. D. R., Whitington, P. F., Neilson, K. A., Suchy, F. J. Delta-4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis. J. Pediat. 124: 234-238, 1994. [PubMed: 8301429]

 Siafakas, C. G., Jonas, M. M., Perez-Atayde, A. R. Abnormal bile acid metabolism and neonatal hemochromatosis: a subset with poor prognosis. J. Pediat. Gastroent. Nutr. 25: 321-326, 1997. [PubMed: 9285385]