Whereas the HFE gene test indicates the risk of eventually developing iron overload, iron studies indicate if iron overload is currently present. Organ damage can be averted with early diagnosis and appropriate venesection therapy, but this is challenging due to the variable, subtle and nonspecific symptoms in early disease.
10,11Ĭ282Y homozygosity confers risk of the multi-organ consequences of iron overload, including liver fibrosis, liver cirrhosis, hepatocellular carcinoma, cardiac arrhythmias, cardiomyopathy, diabetes, arthropathy, hypogonadism and skin hyperpigmentation. 8,10 Even if H63D homozygotes develop elevated serum iron indices, they are unlikely to develop total body iron overload.
C282Y homozygotes are at highest risk of developing total body iron overload whereas C282Y/H63D compound heterozygotes have much lower risk. This mutation has much higher penetrance than the H63D mutation.
9Īpproximately 1 in 200 people of Caucasian race are homozygous for the C282Y mutation. This mutation causes inappropriately increased intestinal iron absorption at a rate 2–3 times greater than normal.8 Similar to type 1 diabetes being a metabolic condition of glucose homeostasis due to insulin deficiency, HH is a metabolic condition of iron homeostasis due to hepcidin deficiency. Hereditary haemochromatosis is an autosomal recessive condition of progressive iron overload, usually due to homozygosity for the C282Y mutation in the HFE gene. Removal of 4 g or more of iron (16 weekly venesections) without developing iron deficiency anaemia indicates iron overload. In HH, total body iron stores can be calculated from the volume of blood removed during weekly venesections. Whole blood contains 250 mg iron per 500 mL.
Iron metabolismĪpproximately 75% of the body's 3–4 g total iron is found within haemoglobin in red blood cells, 10–20% is stored in the protein ferritin and the remainder is found in the iron transport protein transferrin, as well as in myoglobin, cytochromes and as unbound serum iron. Potential harms of frequent venesection therapy for a person without true iron overload include development of iron deficiency anaemia, reinforcement of a suboptimal management strategy for a biochemical abnormality, perpetuation of the myth that a genetic condition affecting family members exists, and the general venesection risks of venous scarring, phlebitis and vasovagal episodes. In the absence of contraindications, patients with elevated SF who do not meet eligibility criteria for therapeutic venesection may become volunteer whole-blood donors every 12 weeks. Options include private pathology providers, public hospitals, haematologists and some GPs. comorbid angina, hepatitis C, cerebrovascular disease) need to be referred elsewhere for therapeutic venesection. Patients meeting therapeutic venesection criteria with contraindications to volunteer blood donation (eg.