Laboratory testing for hemochromatosis

Laboratory testing for hemochromatosis (homozygous HFE C282Y) is primarily based on an increase in SC (saturation coefficient) greater than 60% in men and greater than 50% in women. A high SC should be confirmed in a second blood sample; a normal SC excludes the diagnosis of hemochromatosis.

The second piece of evidence suggestive of this diagnosis is hyperferritinemia. Plasma ferritin correlates quite well with hepatocyte ferritin; hypoferritinemia is a sign of iron deficiency. However, hyperferritinemia, defined by a value of ³ 200 mg/L in women and ³ 300 mg/L in men, certainly suggests the existence of iron overload, but more than nine times out of ten, it indicates a metabolic syndrome; it is also a marker of inflammation and alcoholism.

In practice, elevated SC associated with hyperferritinemia suggests iron overload, most likely related to HFE hemochromatosis; in the course of a metabolic syndrome, SC is normal, in inflammation, SC is low, and in alcoholism, SC is normal or low.

When the SC is > 45% on two occasions, it is necessary to screen for the mutation C282Y in the homozygous state, which indicates the diagnosis of HFE hemochromatosis.

Screening for other mutations (H63D, even in the homozygous state) is not relevant. A C282Y/H63D heterozygous patient does not have hemochromatosis or an increased risk of developing the disease. The patient’s SC may be elevated, but there will be no associated hyperferritinemia and it is not hemochromatosis (or, if ferritin is elevated, it is due to another cause, often a syndrome metabolic).