Noniatrogenic haemochromatosis in congenital dyserythropoietic anaemia type II is not related to C282Y and H63D mutations in the HFE gene: report on two brothers

Abstract

Background: The discovery of the gene responsible for most cases of hereditary haemochromatosis has made it possible to evaluate the role of this gene in iron accumulation in other conditions. Previous observations in patients with various inherited anaemias are suggestive of a role of the haemochromatosis gene in the noniatrogenic form of iron overload that may occur in these conditions.

Methods: We studied two brothers with congenital dyserythropoietic anaemia type II, presenting with marked noniatrogenic iron overload. Young age, familial occurrence, concordance of iron overload, and histology were all suggestive of a genetic basis for the iron overload. A search for C282Y, H63D, S65C, and IVS3 + 1G?T mutations was performed by polymerase chain reaction after extraction of genomic DNA from whole blood.

Results: A search for the C282Y, H63D, S65C, and IVS3 + 1G?T mutations in the HFE gene proved to be negative. Despite the existence of ineffective erythropoiesis with mild anaemia, both patients were treated with regular phlebotomies in order to prevent long-term complications of their iron-overload. This treatment was well tolerated.

Conclusions: 1. C282Y, H63D, S65C, and IVS3 + 1G?T mutations were negative in two brothers with congenital dyserythropoietic anaemia, in whom young age, familial occurrence, concordance of iron overload, and the histological pattern were all suggestive of hereditary haemochromatosis. 2. Treatment with regular phlebotomies, in order to prevent complications of iron overload, was well tolerated despite the existence of mild haemolytic anaemia.