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Hereditary hemochromatosis is a disorder in which iron
is significantly absorbed by the digestive tract and accumulates in body
tissues, which progressively causes diabetes, joint disorders, cardiac
arrhythmia then heart failure, hepatic cirrhosis, skin color change, and
increased risk of cancer.
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Adult Hemochromatosis; Hereditary Hemochromatosis;
Idiopathic Hemochromatosis.
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Genetic disorder of iron metabolism described in 1865 by
Trousseau and named from the Greek words heme (“of the blood”) and chroma
(“color”).
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Fewer than 1:250,000 per year in the general population
but approximately 1:200 people in the United States is believed to have a
mutation necessary for iron overload.
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Autosomal recessive. Males are affected
more severely with an earlier onset. Two mutations in the HFE gene can cause
hereditary hemochromatosis: H63D (less severe and later onset form) and
C282Y. HLA-A3 is found in 78.4% of cases (27% of controls) and HLA-B14
in 25.5% of cases (3.4% of controls). Gene located on 6p21.3, close to
HLA-A locus. (Table H-1)
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The HFE protein is normally expressed in crypt
enterocytes of the duodenum (and the placenta) where it has a predominantly
intracellular localization and forms a stable association with the
transferrin receptor. The HFE protein is believed to modulate the uptake of
transferrin-bound iron from plasma by crypt enterocytes. Impairment of this
function could result in a paradoxical signal in crypt enterocytes, which
causes them to absorb more dietary iron when they mature into villus
enterocytes.
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Usually delayed until adulthood after onset of clinical
symptoms, although screening of family members may lead to early,
asymptomatic diagnosis. Orientation tests include serum ferritin, sideremia,
and liver biopsy for iron staining, which are all consistent with iron
accumulation. Diagnosis established by molecular biology on blood samples
(presence of HFE mutation).
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Symptomatology usually begins at middle age but
may be detected earlier. Early symptoms are nonspecific: weakness, joint and
digestive pains, palpitations, and loss of menstrual periods. Abnormal liver
function tests can be detected earlier, in the absence of other symptoms.
Left untreated, late symptoms appear: bronze skin pigmentation, liver
cirrhosis, or hepatocellular carcinoma, diabetes mellitus,
panhypopituitarism, dysrhythmias, and cardiac failure, joint disorders,
chronic abdominal pain, extreme weakness, and tendency to recurrent
infections.
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Ascertain that ferritin is at the
low end of normal values; if not, postpone surgery (if possible) until this
is achieved. Check ECG for conduction abnormalities; rule out cardiomyopathy
by clinical findings and/or echocardiogram. Evaluate liver function: liver
function test, prothrombin ...