Diagnosis and management of genetic haemochromatosis

Haemochromatosis may be inherited or acquired. The commonest inherited form is HFE-related genetic haemochromatosis (GH). This is associated with homozygosity for the C282Y mutation in the HFE gene. Individuals with GH present in several ways depending upon the severity of iron overload. However, only a small proportion of genetically susceptible individuals develop disease. Diagnosis of GH is based on measurement of transferrin saturation, serum ferritin levels and mutation analysis of HFE. Liver biopsy is not necessary for diagnosis. It is used to establish the severity of liver disease in selected patients. Other complications of iron overload are identified by specific tests. Initial management of GH is by weekly venesection until borderline iron deficiency is achieved. The serum ferritin is then maintained at 50 μg/l by 3–6 monthly venesection. Specific organ damage is managed appropriately. Early diagnosis and treatment before irreversible damage has occurred gives a normal life expectancy. Non-HFE related inherited iron overload may be due to mutations in other iron related genes. Management is along the same lines as for GH, although if venesection is not tolerated, other approaches may be necessary.