[Significance of "minor" genetic mutations in hereditary hemochromatosis: 2 case reports].
We describe a case of homozygosity due to the substitution of aspartic acid with histidine at position 63 of the protein encoded by the gene (known as HFE) associated with hereditary hemochromatosis. Liver biopsy did not disclose stainable iron accumulation; serum ferritin was elevated (639 ng/mL), while the transferrin saturation index was within the normal range (38.1%). As the patient was affected by chronic hepatitis C virus, the high serum ferritin could be attributed to this disease, a frequent occurrence. We also describe a case of heterozygosity for both the substitution of tyrosine with cysteine at position 282 and the substitution of histidine to aspartic acid at position 63 (so-called "compound heterozygosity"). The patient had the typical biochemical abnormalities of iron overload: transferrin saturation index of 53.1% and elevated serum ferritin (658 ng/mL). The removal of > 5 g of iron by phlebotomies did not precipitate iron deficiency. Although the patient refused to undergo liver biopsy, clinical evidence alone enabled a diagnosis of hemochromatosis. These two cases concord with the present scientific orientation, i.e.: 1) homozygosity for the major mutation is associated with the phenotypical (clinical) picture of hemochromatosis, but compound heterozygosity also determines significant iron metabolism abnormalities; 2) homozygosity for the minor mutation does not appear to determine important phenotypical abnormalities.
Maccari
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III Divisione di Medicina Interna e Gastroenterologia, Azienda Arcispedale Santa Maria Nuova di Reggio Emilia.
Plancher
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AC
D000328:Adult; D001706:Biopsy; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D009154:Mutation; D010641:Phenotype; D018962:Phlebotomy
D005293:Ferritins