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