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Previous Volume 341:725-732 September 2, 1999 Number 10 Next

	Full Text PDF Editorial by Tavill, A. S. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background and Methods Hereditary hemochromatosis in adults is usually characterized by mutations in the hemochromatosis (HFE) gene on the short arm of chromosome 6. Most patients have a substitution of tyrosine for cysteine at position 282 (C282Y). We studied a large family from Italy that includes persons who have a hereditary iron-overload condition indistinguishable from hemochromatosis but without apparent pathogenic mutations in the HFE gene. We performed biochemical, histologic, and genetic studies of 53 living members of the family, including microsatellite analysis of chromosome 6 and direct sequencing of the HFE gene.

Results Of the 53 family members, 15 had abnormal serum ferritin levels, values for transferrin saturation that were higher than 50 percent, or both. Thirteen of the 15 had elevated body iron levels, diagnosed on the basis of the clinical evaluation and liver biopsy, and underwent iron-removal therapy. The other two, both children, did not undergo liver biopsy or iron-removal therapy. None of the 15 members had the C282Y mutation of the HFE gene; 5 of the 15 (as well as 5 healthy relatives) had another mutation of this gene, a substitution of aspartate for histidine at position 63, but none were homozygous for it. No other mutations were found after sequencing of the entire HFE gene for all family members. Microsatellite analysis showed no linkage of the hemochromatosis phenotype with the short arm of chromosome 6, the site of the HFE gene.

Conclusions Hereditary hemochromatosis can occur in adults who do not have pathogenic mutations in the hemochromatosis gene.

Source Information

From the Department of Internal Medicine, Università di Modena, Modena (A.P., G.M., C.G., S.C., C.S., F.V.); Ospedale San Giovanni Rotondo, Foggia (A.T., P.G.); and the Department of Gastroenterology, Università di Milano, Milan (D.C., M.F.) — all in Italy.

Address reprint requests to Dr. Pietrangelo at the Department of Internal Medicine, Policlinico, Via del Pozzo 71, 41100 Modena, Italy, or at pietra{at}unimo.it.

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