Information on iron status in inherited disorders of red cell metabolism is so far scanty. Increased serum ferritin (SF) levels have been reported in PK deficiency and related to the concomitance of different factors such as hemolysis, splenectomy and heterozygosity for hereditary hemochromatosis (HH). The hemochromatosis gene (HFE) has not however been extensively investigated in this disease. We evaluated the iron status and searched for mutations C282Y and H63D of the HFE gene (known to be associated with HH) in 35 PK deficient patients (15 M and 20 F; median age 19 range 0-43) from 30 unrelated families. Nine had received multiple transfusions, of whom 8 were splenectomized and underwent chelation therapy. Of the 26 never transfused patients, 4 were splenectomized and 2 (one splenectomized) had needed repeated cycles of iron chelation. Median Hb, reticulocyte number, SF and transform saturation were 8.0 g/dL (range 6.2-9.5), 263xlO'/L (95-1252), 790 ng/L (150-2800) and 83% (23-86) in multitransfused vs. 11.2 g/dL (7.8-15.6), 21 IxlO'/L (89-704), 195 ug/L (58-810) and 43% (19-90) in non transfused patients. In particular, 10 of the 26 untransfused patients displayed markedly increased SF values. SF did not correlate significantly with patients' age and sex, Hb levels, reticulocyte and bilirubin concentration. The screening for mutations C282Y and H63D revealed an abnormal genotype in 10β5 patients. Abnormalities in HFE gene were only found in patients with increased iron burden. In particular, of the 9 multitransfused patients, one was H63D homozygote and 3 H63D hétérozygotes. Of the 10 untransfused, iron overloaded patients, one was C282Y homozygote, one compound hétérozygote for C282Y and H63D and 4 H63D hétérozygotes; the remaining 4 (two of whom splenectomized) had a normal HFE genotype. Interestingly, the compound hétérozygote for C282Y and H63D, the H63D homozygote and one H63D hétérozygote had needed repeated cycles of iron chelation during their life for the progressive raise of serum ferritin in the absence of transfusions. In conclusion, HFE gene mutations, including heterozygosity for H63D are likely to contribute to iron overload in most patients with PK deficient hemolytic anemia. HFE screening may be useful to identify subjects at higher risk of iron overload and to prevent clinical disease complications.
|Issue number||11 PART I|
|Publication status||Published - 2000|
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