Iron status and HFE genotype in erythrocyte pyruvate kinase deficiency: Study of Italian cases

We evaluated the iron status and searched for mutations C282Y and H63D in t he hereditary hemochromatosis gene (HFE) in 34 pyruvate kinase (PK)-deficie nt patients from 29 unrelated families. Nine had received multiple transfus ions. Thirteen of the 25 nontransfused patients displayed increased serum f erritin concentration, in the absence of conditions known to raise this par ameter. HFE genotype was abnormal in 9 of 34 patients. The allele frequency was 1.8% for mutation 845G--->A (C282Y) and 16.1% for mutation 187C-->G (H 63D). Nontransfused subjects with abnormal genotype had serum ferritin and transferrin saturation values significantly higher than those with wild-typ e genotype. Of the 12 adult nontransfused patients with increased iron stat us parameters, 1 was C282Y homozygous, 1 compound heterozygous for C282Y an d H63D, 3 H63D heterozygous, and 7 had a normal HFE genotype. Serum ferriti n and transferrin saturation were not related to hemoglobin, reticulocytes, and bilirubin concentration. At multivariate analysis serum ferritin was i ndependently associated with age and gender, but not with splenectomy and H FE genotypes. The retrospective evaluation of the iron status profile of 10 patients (3 with abnormal and 7 with wild-type HFE genotype) with at least 10 years follow-up showed that overt iron accumulation requiring iron chel ation had occurred only in the 3 patients (2 of whom were splenectomized) w ith the mutated HFE gene. (C) 2001 Academic Press.