Final Diagnosis -- Hereditary Hemochromatosis







In the absence of any other cause of iron overload, hereditary hemochromatosis (HH) is the most likely diagnosis in this patient. HH is an autosomal disorder of iron metabolism with an incidence of 1:220 in populations of Northern European, Caucasian descent and a gene frequency as high as 1:9, or 11 percent. Total body iron concentration in normal individuals is 2 to 6 gm. Individuals with HH accumulate iron at a rate of 0.5 to 1.0 gm per year and may exceed total iron concentrations of 50 gm. Symptoms of HH usually develop after 20 gm of iron has accumulated. Thus, men tend to become symptomatic in middle age and women after menopause.

Alcohol can accelerate the effects of iron overload. Chronic alcoholics can exhibit hepatic fibrosis or cirrhosis almost twice as frequently as non-alcoholic men. It is interesting to note that about 10 percent of alcoholics with cirrhosis have extensive iron deposition, and this is roughly the frequency of heterozygosity for HH. The iron deposition associated with chronic alcoholism, however, is typically limited to the liver and not seen extensively in other organs.

Iron deposition in major organs, presumably by direct toxic effect, results in cirrhosis, diabetes mellitus, skin pigmentation, polyarthropathy, and hypogonadotrophic hypogonadism. Cardiac involvement may take the form of arrhythmias, restrictive cardiomyopathy, or as in this case, dilated cardiomyopathy. All of these complications, however, are much more commonly seen in persons who do not have HH, so without a family history or iron studies, HH will not be suspected. It should be noted that, thoughout most of human history, the average lifespan was not great enough to allow manifestation of HH, so the appearance of persons with complications of HH is a relatively modern phenomenon.

The diagnosis of HH depends upon documenting excessive iron storage. This can be accomplished by measuring serum iron and iron binding capacity with calculation of percent saturation. The iron and the percent saturation should be high. Serum ferritin is also a good indicator of the amount of storage iron in the body. The "gold standard" to establish the diagnosis and severity of disease is liver biopsy with quantitation of the amount of iron.

The treatment of HH is simple: therapeutic phlebotomy to remove excess iron. The most common causes of death in individuals with HH are hepatocellular carcinoma associated with cirrhosis, hepatic failure, and cardiac failure. There appears to be a subgroup of young patients who present with severe cardiac involvement and in whom outcome is poor as a result of congestive heart failure if they remain untreated. In one series of patients who presented with cardiomyopathy associated with hemochromatosis, therapeutic phlebotomy improved the prognosis in 70 percent; untreated patients had a worsening of their condition and mean survival of only one year.

The gene for HH is located on chromosome 6. This locus is associated with the HLA A-3 antigen. Seventy percent of HH individuals have the HLA A-3 genotype, whereas it is present in only 25 percent of normal individuals. Screening siblings or first degree relatives by serum transferrin saturation or HLA studies is important to identify relatives at risk. Early diagnosis and institution of therapeutic phlebotomy can prevent the above manifestations and normalize life expectancy, but once organ damage is established, many of the manifestations are irreversible.


  1. Porter J, et al. Haemachromatosis presenting as congestive cardiac failure. British Heart Journal, January; 73(1):73-75, 1995.

  2. Loreal O, et al. Liver fibrosis in genetic hemachromatosis, respective roles of iron and non-iron related factors in 127 homozygous patients. Journal of Hepatology; 16:122-127, 1992.

  3. Phatak FD, et al. Management of hereditary hemachromatosis. Blood Reviews; 8(4):193-198, 1994.


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