Primary hemochromatosis is a genetically determined autosomal recessive disorder characterized by the excessive accumulation of body iron, most of which is deposited in the parenchymal cells of various organs.
a,-Antitrypsin deficiency is characterized among others by defective secretion of a,-antitrypsin from liver cells. Whereas the risk of cirrhosis is increased in homozygoua patients (PI ZZ) and possible in heterozygous patients (non-PI MM) as well, a greater risk for hepatocellular carcinoma has been suggested only in homozygoua patients.
Because these two metabolic disorders are relatively common, it has been difficult to determine whether they are associated with each other. In this study, we tried to determine the relationship between these two disordersusing the case material seen at the University of Pittsburgh during a 7-yr period.
We studied 15 patients with genetic hemochroma-to&. a,-Antitrypsin quantitation and phenotyping were performed in each case using standard methods.
The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds ratio and f tests were used to measure the relative risk and significance of association, respectively.
Eleven patients (73%) were found to be PI M and four (27%) were identified as being heterozygotes: three (20%) were PI MZ, and one (7%) was PI MS. The prevalence of the PI MS phenotype was similar to that in the general population (7% vs. 6.4%; NS). The PI MZ phenotype, however, was statistically more common in patients with hemochromatosis than in the general population (20% vs. 2.2%; p < 0.004). The odds of having hemochmatosis among PI MZ patients is increased 11-fold (odds ratio = 11.25; 95% confidence intervak 1.95, 44.23). The mean serum level of a,antitrypsin and the occurrence of hepatocellular carcinoma was similar in the patients with the PI M and non-PI M phenotypes.
It can be concluded that abnormal a,-antitrypsin alleles are seen more frequently in patients with genetic hemochmatolsis than in the general population. Their coexistence may contribute to the earlier