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We have read with great interest the excellent review entitled: "Genetics of familial intrahepatic cholestasis syndromes" by van Mil S. W. C. and collaborators, and published in the last issue of Journal of Medical Genetics.  In an attempt to complete this very exhaustive
review, we wished to make a few comments:
- concerning delta4-3-Oxosteroid-5beta reductase (AKR1D1) deficiency, since t...
- concerning delta4-3-Oxosteroid-5beta reductase (AKR1D1) deficiency, since the human gene (AKR1D1, also named SRD5B1) was cloned, two recent publications [2,3] report 5 SRD5B1 mutations responsible for delta4-3-
Oxosteroid-5beta reductase deficiency in 5 patients. These data confirm that the disease is transmitted in a recessive autosomal pattern, and show that when delta4-3-Oxosteroid-5beta reductase deficiency is suspected on the basis of mass spectrometry analysis of urinary bile acids, diagnosis can be confirmed by molecular biology technology. This new diagnostic tool is important because patients with other severe liver diseases may present
an abnormal concentration of bile acids with 3-oxo-delta4 nuclear structure secondary to liver failure and not due to genetically determined enzyme defect. So far it is admitted that only patients with a primary genetic defect may benefit from early primary bile acid therapy in order
to try to correct liver failure and to avoid liver transplantation.[2,3]
- concerning HSD3B7 deficiency, in our experience the patients never exhibit pruritus at presentation and during the disease course. Iatrogenic pruritus may occur under cholic acid therapy in case of accidental overdose. We therefore believe that absence of pruritus in presence of
cholestasis features is a strong sign indicating a possible primary bile acid synthesis defect.[5,6] Since the first report in 2000 of a patient harbouring homozygous HSD3B7 mutation, additional mutations have been identified in 15 patients.
We hope these additional informations will favourably complete this excellent review.
Emmanuel Gonzales, M. D.
Emmanuel Jacquemin, M. D., Ph. D.
Pediatric Hepatology, Bicêtre Hospital, AP-HP, University of Paris XI,
Paris , France