Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect

Abstract

This paper outlines the Danish aspects of HFE-hemochromatosis, which is the most frequent genetic predisposition to iron overload in the five million ethnic Danes; more than 20,000 people are homozygous for the C282Y mutation and more than 500,000 people are compound heterozygous or heterozygous for the HFE-mutations. The disorder has a long preclinical stage with gradually increasing body iron overload and eventually 30% of men will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease and diabetes. Subsequently the disease may progress into irreversible arthritis, liver cirrhosis, cardiomyopathy, pancreatic fibrosis and osteoporosis. The effective standard treatment is repeated phlebotomies, which in the preclinical and early clinical stages ensures a normal survival rate. Early detection of the genetic predisposition to the disorder is therefore important to reduce the overall burden of clinical disease. Population screening seems to be cost-effective and should be considered.

Keywords: Arthritis; Diabetes mellitus; HFE-associated hemochromatosis; Hemochromatosis type 1; Hepatocellular carcinoma; Hereditary hemochromatosis; Iron overload; Liver cirrhosis.

Figure 1

Diagnostic and therapeutic algorithm (simplified) in the assessment of HFE-hemochromatosis.

Figure 2

A 55-year-old woman with hemochromatosis and liver fibrosis. Due to fatigue, the patient had been taking iron tablets for several years without having a checkup of her body iron status. After 22 phlebotomies over a period of 300 days, the iron excess was finally removed.