REPLY
Hemochromatosis and Diabetes Mellitus
Dario Conte, MD;
Mirella Fraquelli, MD; and
Agostino Colli, MD
1 October 1998 | Volume 129 Issue 7 | Page 587
IN RESPONSE:
Hegele and colleagues' data are most interesting. The community of the Oji-Cree screened for the HFE C282Y mutation is an isolated population in which intermarriage is common; this could explain the high prevalence of type 2 diabetes and the low frequency of the HFE C282Y allele compared with the worldwide and European frequencies.
In addition, although most series have reported a frequency of homozygosity for the major HFE mutation of greater than 85% [1], in Southern France and Italy the frequency is only about 70%; this indicates a marked genetic heterogeneity for genetic hemochromatosis [2, 3]. The phenotypic expression of this disease varies widely because of possible combined effects of genetic and environmental factors. For instance, the ancestral haplotype, which is more frequent in populations of Celtic origin, is associated with a higher degree of iron overload and a more severe phenotype [4]. Consequently, although the discovery of the HFE gene led to major advances in knowledge of the disease, diagnosis and screening (at least in our geographic area) should be based primarily on transferrin saturation, and serum ferritin analysis screening for the HFE gene should be a second-step diagnostic tool.
The message in our report-that screening patients with type 2 diabetes is useful because it identifies many cases of undiagnosed genetic hemochromatosis-is reasonable in Italy and probably in most areas with an elevated prevalence of this disease. It may not be reasonable in areas in which the prevalence is significantly lower than in Italy. Furthermore, the type of genetic hemochromatosis screening to be used may vary in different areas according to the frequency of HFE homozygotes.
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Author and Article Information
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IRCCS, Ospedale Maggiore; 20122 Milano, Italy
Ospedale Civile di Morbegno; 23017 Morbegno, Italy
1. Bacon BR. Diagnosis and management of hemochromatosis. Gastroenterology. 1997; 113:995-9.
2. Piperno A, Sampietro M, Pietrangelo A, Arosio C, Lupica L, Montosi G, et al. Heterogeneity of hemochromatosis in Italy. Gastroenterology. 1998; 114:996-1002.
3. Borot N, Roth MP, Malfroy L, Demangel C, Vinel JP, Pascal JP, et al. Mutations in the MCH class I-like candidate gene for hemochromatosis in French patients. Immunogenetics. 1997; 45:320-4.
4. Piperno A, Arosio C, Fargion S, Roetto A, Nicoli C, Girelli D, et al. The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients. Hepatology. 1996; 24:43-6.
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