Identification of homozygous hemochromatosis subjects by measurement of hepatic iron index.

The value of measurement of hepatic iron concentration and determination of the hepatic iron index in distinguishing homozygotes from heterozygotes for hemochromatosis was examined. The study group included 42 homozygotes with an unequivocal diagnosis of hemochromatosis and six individuals who had initial equivocal results but were established as homozygous after extensive follow-up. These were compared with 15 heterozygotes with no sign of increasing body iron stores who had undergone liver biopsy because of an initial suspicion of raised iron levels. In these subjects a hepatic iron concentration of greater than 75 mumol/gm dry weight was clearly indicative of homozygous hemochromatosis. Body iron accumulation was age-related both in homozygotes and in these heterozygotes with mild biochemical abnormalities (r = 0.476; p = 0.001 and r = 0.689; p = 0.01, respectively), with a rate of accretion of approximately 5 mumol/gm dry weight/year in homozygotes and 0.9 mumol/gm dry weight/year in heterozygotes. Thus, lower values in young subjects may be consistent with homozygosity, and higher values in older individuals are consistent with heterozygosity. To overcome this problem, the hepatic iron index (hepatic iron concentration divided by age in years) was analyzed and found to separate the two groups effectively, with no homozygote having an index of less than 1.9 and no heterozygote having an index of greater than 1.5. These results in a series of patients who have been followed for a median of 3 yr (range = 1 to 30 yr) validate the use of the hepatic iron index to discriminate hemochromatosis homozygotes from heterozygotes with raised levels of serum ferritin, transferrin saturation or both.