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congenital defect in bile acid synthesis type 2

MIM.235555 7q32-q33

Tuesday 17 May 2011

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#]