Background Hereditary Hemochromatosis (HH) is a genetic disorder in which mutations of the HFE gene, and less frequently in the transferring receptor 2 (TFR2) gene, result in an increase in intestinal iron absorption. Clinically this disorder manifests itself in the deposition of iron in tissues such as the liver, heart and pancreas. Almost one half of HH patients will develop arthritis if left untreated.
Objectives Because joint pain and swelling are prominent symptoms of HH, many patients find their way into the rheumatology practice before the disease is diagnosed.
In order to determine the incidence of HH in our practice, we have routinely investigated iron metabolism in new patients over the last 5½ years.
Methods We measured in serum concentrations of ferritin, transferrin and iron in 10,035 patients and calculated the iron-transferrin saturation. Patients were tested for HH by determining mutations of the HFE gene C282Y and H63D if the iron saturation was >45% and ferritin levels were elevated. In cases where iron overload persisted in the absence of HFE mutations, the non HFE genes homojuvelin, herceptin, transferrin, transferrin receptor and ferroportin were analyzed for possible mutations. In patients that had been treated by phlebotomy or iron chelation therapy the liver iron concentration was measured using the MRI-based FerriScan technology.
Results Of patients showing an iron overload (iron transferrin saturation >45% and elevated ferritin), 42 were diagnosed as having HH by genetic analyses: 24 C282Y homozygotes, 7 H63D homozygotes, 7 compound heterozygotes C282Y/H63D, 1 homozygote for the non-HFE-gene ferroportin, 2 homozygotes for the transferrin receptor 2, and 1 H63D/transferrin receptor 2 heterozygote. All patients suffered from arthralgias and about one half had typical HH-arthopathy of the metacarpalia-phalangeal joints II and III of the hands. Most patients could be treated successfully by phlebotomy or iron chelation therapy. The effect of these treatments could be monitored by measuring the reduction in liver iron concentration using FerriScan MRI.
Conclusions HH is an important differential diagnosis in cases with undifferentiated joint pain. Parameters of iron metabolism should be routinely determined in these patients.
Disclosure of Interest None declared