ࡱ> FHE bjbjSS .$11 00000DDDD$hD>uuu=======$a@C\=0uuuuu=00 >8u 00=u=9 =`H\Q :"=C><>;oCoCD =oC0 =uuuuuuu==uuu>uuuuoCuuuuuuuuu : Haemochromatosis Hereditary haemochromatosis (HH), genetic haemochromatosis Introduction HH is an adult onset, treatable, inherited disorder of iron metabolism causing excessive absorption of dietary iron with progressive iron overload. If untreated deposition of iron in tissues eventually results in cirrhosis of the liver, diabetes mellitus, skin pigmentation and testicular failure. It is caused by mutations in the HFE gene on chromosome 6. In North European populations, ~1 in 200 people are homozygous for the common C282Y mutation in HFE giving a carrier frequency of 1 in 10. HH is not fully penetrant and many homozygous individuals will never develop clinically significant disease. Clinically significant disease is ten times more common in men than in pre-menopausal women because menstruation and pregnancy deplete iron stores in women. Genetics HH type 1 is an autosomal recessive (AR) disorder. There are two common gene mutations: C282Y and H63D. Approximately 90% of patients with HH are homozygous for C282Y; a further 4% are compound heterozygotes for C282Y/H63D. H63D homozygotes do not develop HH. Management in primary care Diagnostic testing Investigations in primary care Iron studies, including serum Fe, ferritin (reflects total body Fe stores) and transferrin saturation (best screening test). Ferritin. In normal subjects, ferritin concentrations of >300mg/L for men and postmenopausal women and >200mg/L for premenopausal women indicate elevated iron stores (levels may vary between different labs). Transferrin saturation. If transferrin saturation >50%, repeat on a fasting morning sample. Fasting transferrin saturation >55% (men) and >50% (women) is abnormal and indicates Fe accumulation. Normal values are 20-40%; carriers may have intermediate levels and genotyping may be helpful in determining significance. DNA for HFE genotyping after appropriate discussions and with patient consent Management of those with HH genotypes, e.g. all C282Y homozygotes or C282Y/H63D with abnormal iron studies For individuals with ferritin of >1000mg/L or raised ALT Refer to a hepatologist For individuals with ferritin of <1000mg/L and normal ALT Minimal risk of liver fibrosis, but if ferritin >400mg/L will need therapeutic venesection (refer to Hepatology or local venesection service, if available, aiming for ferritin of 50mg/L). For those with ferritin of 200-400mg/L, reassure that they are unlikely to suffer any ill effects and suggest that they donate blood up to 4 times a year via the National Blood Transfusion Service in order to prevent further iron overload. Monitor annually to look for iron accumulation. For those with ferritin <200mg/L fully reassure and monitor 2-5 yearly to look for iron accumulation. If ferritin rises, consider blood donation or venesection. Cascade Screening of family members This should be offered to the adult first degree relatives of an affected individual. Adult first-degree relatives should have HFE mutation analysis and iron indices (serum Fe, ferritin and transferrin saturation). This can be requested by primary care teams. Anyone found to have an HH genotype should be managed as above. Genetic testing for HH is carried out by the North West Thames Regional Genetic Service. Please see user guide for further information:  HYPERLINK "http://www.lnwh.nhs.uk/services/a-z-services/g/genetics/laboratory-services/" http://www.lnwh.nhs.uk/services/a-z-services/g/genetics/laboratory-services/ MN[bpq &   # & 0 B D E F J O Q T ] f L l ϯϷϯϷϷπxh"CJaJh"h"CJaJhJhCJaJh CJaJh"hJhCJaJh6CJaJh(CJaJh CJaJhCJaJhpFCJaJh=CJaJh"hDCJaJhD6CJaJhDCJaJh hD5CJ(aJ*MN[ P Q \ ] f k l $da$gd" $da$gd=$ & Fda$gd=$ & Fda$gd  $da$gd 7 ? 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