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Previous Volume 335:1799-1805 December 12, 1996 Number 24 Next

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ABSTRACT

Background Ten percent of whites are heterozygous for the HLA-linked hemochromatosis mutation. We performed a cross-sectional analysis of 1058 genotyped heterozygotes to define the effects of age and sex on the phenotype.

Methods The heterozygous genotype was assigned to 505 male and 553 female members of 202 pedigrees, each with an HLA-typed homozygous proband. We measured serum iron, transferrin saturation, and ferritin in all heterozygotes and in 321 genetically normal subjects (unaffected family members or spouses of family members). Liver biopsies were performed in a subgroup of heterozygotes.

Results The mean serum iron concentrations and transferrin-saturation values were higher in heterozygotes than in normal subjects and did not increase with age. Initial transferrin-saturation levels exceeding the threshold associated with the homozygous genotype were found in 4 percent of male and 8 percent of female heterozygotes. The geometric mean serum ferritin concentration was higher in heterozygotes than in normal subjects and increased with age. Higher-than-normal values were found in 20 percent of male and 8 percent of female heterozygotes. The clinical and biochemical expression of hemochromatosis was more marked in heterozygotes with paternally transmitted mutations than in those with maternally transmitted mutations. Liver-biopsy abnormalities were generally associated with alcohol abuse, hepatitis, or porphyria cutanea tarda.

Conclusions The phenotype of persons heterozygous for hemochromatosis differs from that of normal subjects, but complications due to iron overload alone in these heterozygotes are extremely rare.

Source Information

From the Departments of Internal Medicine (Z.J.B., L.M.G., C.Q.E., J.P.K.) and Human Genetics (L.B.J.), University of Utah School of Medicine, and Latter Day Saints Hospital (C.Q.E.) — both in Salt Lake City.

Address reprint requests to Dr. Kushner at 4C-416, Division of Hematology–Oncology, University of Utah School of Medicine, Salt Lake City, UT 84132.

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