Iron overload
Iron overload is the pathological state in which total body stores of iron are increased, often with organ dysfunction as a result of iron deposition.
Causes
- Primary (genetic) haemochromatosis (GH) is an autosomal recessive condition associated with excessive iron absorption. Ninety per cent of cases are homozygous for a mutation in the HFE gene. Rarely, GH is caused by mutation of the hepcidin, hemojuvelin, or transferrin receptor 2 gene. All these proteins are involved in hepcidin synthesis (see Fig. 9.2) and all cases show low serum levels of hepcidin.
- African iron overload; dietary and genetic components.
- Excess dietary iron.
- Ineffective erythropoiesis with increased iron absorption (e.g. thalassaemia intermedia) due to inappropriately low levels of hepcidin.
- Repeated blood transfusions in patients with severe refractory anaemia, e.g. thalassaemia major, myelodysplasia. Each unit of blood contains 200–250 mg iron.
Clinical features
- These are mainly caused by organ dysfunction as a result of iron deposition (Fig. 10.1).
- Cardiomyopathy gives rise to dysrhythmias and congestive heart failure, major causes of death.
- Growth/sexual development is reduced in children; delayed puberty, diabetes mellitus, hypothyroidism and hypoparathyroidism are frequent.
- The liver may show haemosiderosis or cirrhosis. The liver abnormality in transfusional iron overload is, however, often a result of hepatitis B or C infection. Hepatocellular carcinoma is a complication of cirrhosis.
- Excessive melanin skin pigmentation.
- Excessive infections.
- Arthropathy in genetic haemochromatosis caused by pyrophosphate deposition.
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