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Hereditary Haemachromatosis

Hereditary Haemachromatosis. Dr Eileen C Kelleher Haematologist eckelleher@bonsecours.ie October 1st 2016. Haemachromatosis. Inherited disorder resulting from an inborn error of metabolism, which leads to progressive iron overload, of the parenchymal cells of the liver, pancreas and heart

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Hereditary Haemachromatosis

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  1. Hereditary Haemachromatosis Dr Eileen C Kelleher Haematologist eckelleher@bonsecours.ie October 1st 2016

  2. Haemachromatosis • Inherited disorder resulting from an inborn error of metabolism, which leads to progressive iron overload, of the parenchymal cells of the liver, pancreas and heart • In its fully developed stage, organ structure and function are impaired

  3. Haemachromatosis • excessive intestinal absorption of dietary iron • pathological increase in total body iron stores • humans have no means to excrete excess iron • ( except menstuation and pregnancies) • excess iron accumulates in tissues and organs disrupting their normal function • most susceptible organs include the liver, adrenal glands, heart, skin, gonads, joints and pancreas

  4. ‘Haemochromatosis Gene’, or HFE • ‘HaemochromatosisGene’, or HFE, revealed by Feder and colleagues in 1996 • Pathogenesis had been unravelled ! • since emerged, this was just one piece of a complex puzzle • that is still being assembled • individuals screened for pathogenic mutations • not all those with mutations came to harm or developed HH • the disease has incomplete penetrance

  5. The HFE gene • C282Y substitution of cysteine for tyrosine the commonest • 98% of Irish HH genoptype • H63Daspartate for histidine substitution • Homozygosity for the C282Y mutation • confers the greatest risk of developing HH • ‘Compoundheterozygotes’ with shared C282Y and H63D mutations • May develop disease • H63D homozygotes • Rarely develop clinical disease • To be diagnosed with HH, an individual requires both • HFE genotype • objective clinical manifestations of iron overload (phenotype)

  6. ‘HaemochromatosisGene’, or HFEPrevalence • Commonest genetic disorder in Caucasions • Particularly of northern European and Celtic decent • Homozygous 1 in100 to 1 in 200 • Carrier 1in 8 to 1 in 10 • Ireland • 93% of HH patients are C282Y • estimate a prevalence of C282Y homozygosis 1 in 83 persons • indicating that over 25,000 Irish adults are at risk for developing HH • Carrier frequency 1 in 5 to 1 in 10

  7. HFE penetrance- phenotype • Despite this high prevalence • approximately 30 % of males and 20% of females who are C282Y homozygous will actually develop clinically-significant complications related to iron overload • Irish studies indicate that these figures could be higher in a homogeneous Irish population.

  8. Phenotype • Age • Sex • Blood loss • Pathological and physiological • Blood donations • Dietary iron • Alcohol • Hepatitis B & C • Obesity • Dietay supplements • Iron and Vitamin C

  9. Signs and Symtoms • Organs commonly affected • liver, heart , endocrine glands (pituitary, pancreas) • may present with the following clinical syndromes • Cirrhosis of the liver • Diabetes • Cadiomyopathy • Arthritis • Gonadal failure • Pigmentation of the skin • Joint pain and bone pain

  10. Investigations • Serum Ferritin • > 300 mg/l for men and post menopausal female • > 200 mg/l for pre menopausal female • Iron over load • But not exclude HH genotype • Transferrin saturation and Ferritin (Fasting) • both elevated good positive predictive of HFE • Normal Ferritin is good predict • HFE genotyping

  11. Investigations • U & E • Liver profile • Blood sugar and Hb A1c • Lipds • ECG • CxR • U/S liver, Liver biopsy or MRI liver if abn LFTs, alpha feto protein

  12. Management • Dietary and oral supplements advice • Venesections • Alcolol intake

  13. Management • Venesections • When evidence of iron overload • Rather than waiting for symtoms • 400-500mls per occasion • Some much less • Until ferritin 50 -100 ng/ml • Every 1-2 weeks • Usual maintenance 3-4 per year

  14. Venesections • Takes approxmately 30 minutes on the chair • Ensure drink 500 ml fluid within 1 hour before hand • Rest for 30-60 minutes after venesection • No strenous work for following 24 hours • Depends on the age and co morbidities of the patient • Consent

  15. Venesections • Bon Secour Hospital • Phlebtomy Department • Una Howard and team

  16. Venesection • IBTS • Patient is stable on 3-4 venesections per year • Meets the criteria for voluntary blood donations • No complications of the HH

  17. Screening • Family members • Serum Ferritin +/- Transferrin Saturation • Iron overload present • Genotyping

  18. Conclusion • Inherited disorder of Iron overload • Commonest genetic disease among Caucasions, especially Celtic, particularly Ireland • Patients are predominantly men • Early detection and treatment prevents organ damage and normal life expectancy • Amenable to diagnosis, treatment

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