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HEMOCHROMATOSIS Wendy Graham, MD, CCFP Academic ½ Day November 25, 2003.

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Presentation on theme: "HEMOCHROMATOSIS Wendy Graham, MD, CCFP Academic ½ Day November 25, 2003."— Presentation transcript:

1 HEMOCHROMATOSIS Wendy Graham, MD, CCFP Academic ½ Day November 25, 2003

2 Pathophysiology Inborn error in iron metabolism Increased iron absorption from the diet Iron overload Eventual fibrosis and organ failure  Cirrhosis  Cardiomyopathy  Diabetes  Hypogonadism

3 Hereditary Hemochromatosis Autosomal recessive disorder Hemochromatosis gene (HFE) Most common single gene disorder 1/250 – 1/300 white persons is homozygous for the gene mutation 1/10 carrier for mutation 60-93% with disorder homozygous for the mutation C282Y (a cysteine–to-tyrosine substitution) Also C282Y/H63D compound heterozygosity


5 Iron Overload Net absorption of 3-4 mg/day Accumulation of 500 to 1000 mg iron/yr Clinical manifestations often occur after age 40 OR when stores are 15-40 g

6 Clinical Manifestations Influenced by  Age  Sex  Dietary iron  Alcohol  Blood loss in menstruation and pregnancy  Unknown factors Alcohol abuse and Hepatitis C accelerate Classic description: cutaneous hyperpigmentation and diabetes in a patient with cirrhosis

7 Reversible Manifestations Heart: cardiomyopathy, conduction disturbances Liver: abdominal pain, elevated LFTs, hepatomegaly (95%) Skin: bronzing (melanin deposition), gray pigmentation (iron deposition) Infection (Vibrio vulnificus, Listeria monocytogenes, Pasteurella pseudotuberculosis)

8 Irreversible Manisfestations Liver: cirrhosis, hepatocellular carcinoma (most common cause of death) Pituitary gland: gonadotropin insufficiency leading to secondary hypogonadism Pancreas: diabetes mellitus (30-60%) Thyroid: hypothyroidism Genitalia: primary hypogonadism Joints: arthropathy in MCPs (20-70%), pseudogout


10 Women & Hemochromatosis Homozygosity is as common as in men Symptomatic disease 10x less frequent Presentation is later in women Why?  Physiological blood loss in women and higher iron intake in men

11 Diagnosis Combination of criteria  Clinical  Laboratory  Pathologic Elevated serum transferrin saturation >45%(earliest abnormality) and an elevated serum ferritin Caution serum ferritin = acute phase reactant Confirmation = ‘gold standard” = liver biopsy (also defines extent of disease)

12 Treatment Reserved for evidence of iron overload/complications Desferrioxamine (DFO) ineffective Avoid iron supplements, red meat Avoid alcohol and tobacco Avoid handling of raw seafood Trestment = phlebotomy

13 Phlebotomy Removal of 500 ml of blood Removes 250 mg iron Do weekly until iron depletion  Hgb < 120  Ferritin < 50  Transferritin saturation < 50%  2-3 years may be required to remove >20g Long term maintenance about once every 3 months

14 Genetic Testing Gene on the short arm of chromosome 6 Point mutations C282Y and H63D HFE gene test in adult family members of an identified case Should replace HLA typing Pretest counselling (insurance, employment…) Gene testing not recommended < 18 years Done on whole bloold sample $200 U.S.

15 Screening ?population screening  Looking @ WHO criteria likely cost effective  Not yet endorsed because need more information on disease burden and expression of disease Ongoing study in Canada and U.S of 100 000 Currently screen in patients who have:  Chronic liver disease  Signs and symptoms associated with the disease  A family history of iron overload


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