hemochromatosis wendy graham, md, ccfp academic ½ day november 25, 2003
TRANSCRIPT
HEMOCHROMATOSIS
Wendy Graham, MD, CCFP
Academic ½ Day
November 25, 2003
Pathophysiology
Inborn error in iron metabolism Increased iron absorption from the diet Iron overload Eventual fibrosis and organ failure
Cirrhosis Cardiomyopathy Diabetes Hypogonadism
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
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
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
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)
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
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
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)
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
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
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.
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