Diagnosing Hemochromatosis

Hemochromatosis is a notoriously underdiagnosed disorder, with numerous examples of patients going decades with symptoms masquerading with such diversity as to include multisystem disease, liver disease, immune deficiency, and rheumatologic disorders. Since up to 10% of whites are heterozygous for hemochromatosis, any secondary biochemical or clinical aberrations would be potentially clinically relevant.

In 1058 males and females heterozygous for hemochromatosis, serum iron, transferrin saturation, and ferritin were measured. Liver biopsy was performed in 39 subjects.

Mean serum iron and transferrin saturation were higher in heterozygotes than in normal subjects, and in a minority of cases, the transferrin saturation exceeded the threshold level (62% saturation) associated with homozygous hemochromatosis. Twenty percent of men and 8% of women over 31 years of age in the study had a serum ferritin greater than the 95th percentile. Although six liver biopsy specimens demonstrated liver damage, in five of six cases associated disease (porphyria, hepatitis, alcoholism) accounted for the pathology.

The authors conclude that most heterozygotes will not be misclassified as homozygotes on the basis of biochemical markers. When it is not possible to determine with certainty whether the patient is heterozygous or homozygous, therapeutic phlebotomy to euferremia is advocated.

Bulaz Z, et al. N Engl J Med 1996; 335:1799-1805.