HEMOCHROMATOSIS
Section snippets
DEFINITIONS, CAUSES, AND CLASSIFICATION OF IRON OVERLOAD
States of iron overload in the human can result from several disorders, some inherited and some acquired, and may be classified accordingly.
Nomenclature for Iron Overload States Hereditary hemochromatosis
- A
HFE-associated hereditary hemochromatosis
- •
C282Y homozygosity
- •
C282Y/H63D compound heterozygosity
- •
- B
Non– HFE-associated hereditary hemochromatosis
- C
Juvenile hemochromatosis
- D
Autosomal dominant hemochromatosis
- E
Acquired iron overload
- A
Iron-loading anemias
- •
Thalassemia major
- •
Sideroblastic anemia
- •
Chronic
- •
- A
PATHOPHYSIOLOGY OF IRON OVERLOAD
A detailed account of iron metabolism is beyond the scope of this article, but newer concepts of iron metabolism and iron absorption resulting from the discovery of HFE and its functions are summarized. Iron balance is regulated by iron absorption,20 which in turn is reciprocally regulated by the level of body iron stores.22 In hereditary hemochromatosis (HHC), the enhanced net absorption of 3 to 4 mg/d results in the accumulation of 500 to 1000 mg of iron/y during adult life. Increased
Prevalence and Mode of Inheritance
HFE-associated hereditary HC is an inherited autosomal recessive trait and is the most common inherited liver disease in Europeans (Table 1). Studies using biochemical markers of iron overload conducted in Australia,48 South Africa,53 Italy, and the United States77 have found a very high prevalence, between 0.22% and 0.95%. Reliance on biochemical expression infers complete phenotypic expression in affected individuals. In a screening study of more than 3000 subjects in Busselton, Western
OTHER CAUSES OF HEREDITARY HEMOCHROMATOSIS
A list of causes of iron overload with organ damage is given at the beginning of this article. Clearly, because the C282Y mutation has only recently been identified, understanding is continuing to evolve. With 16 of 75 (21%) Italian patients with HHC shown not to have the C282Y mutation, Carella et al19 have presented evidence for a second cause of hemochromatosis linked to the HLA-A locus. Worwood et al86 also describe six patients with HHC who lack the C282Y mutation. They suggest that other
ROLE OF THE HEREDITARY HEMOCHROMATOSIS MUTATIONS AND IRON IN OTHER DISEASES
In addition to the direct complications of tissue iron excess that occur as manifestations or complications of HHC, increased body iron stores have been implicated in the pathogenesis of several other disease states.
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Address reprint requests to Lawrie W. Powell, PhD, MD, The Queensland Institute of Medical Research, The Bancroft Centre, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia 4029, e-mail: [email protected]