Hereditary haemochromatosis

What it is

Hereditary hemochromatosis is a genetic disorder of iron regulation and subsequent iron overload. It is an autosomal-recessive disorder in which intestinal absorption of iron is increased, with iron deposition in multiple organs. A secondary hemochromatosis also exists, and it is transfusion-related.

How it presents

Symptoms are often nonspecific early on, but manifestations of iron overload eventually occur. The most common symptoms are erectile dysfunction, fatigue, destructive arthropathy of the second and third MCP joints with distinctive hook-like osteophytes, and OA involving unusual joints such as the shoulders, ankles and elbows. Less commonly there is diabetes, HF, hyperpigmentation with skin bronzing, and panhypopituitarism.

How it is diagnosed

The diagnosis should be suspected in patients with liver disease, or with abnormal iron studies indicative of iron overload. The most appropriate screening test is fasting serum transferrin saturation. Some guidelines suggest the diagnosis when the value is >60% in men or >50% in women, and others suggest >55% for all patients. C282Y homozygous or C282Y/H63D compound heterozygous HFE genotypes are diagnostic of hemochromatosis. A liver biopsy can confirm the diagnosis and the degree of fibrosis.

Liver biopsy is indicated when ferritin is markedly elevated, above 1000 ng/mL, to assess the degree of fibrosis, even with a diagnostic genotype. Two things go with the numbers. Advanced liver disease commonly causes an elevated ferritin level, but the iron saturation is usually normal; and a nondiagnostic HFE genotype does not rule out a diagnosis of hemochromatosis. First-degree relatives of patients with hemochromatosis should undergo screening.