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Hereditary hemochromatosis is an iron overload disorder that can lead to the impairment of multiple organs and is caused by mutations in one or more different genes. Type 1 hemochromatosis is the most common form of the disease and results from mutations in the HFE gene. Juvenile hemochromatosis (JH) is the most severe form, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP). The autosomal dominant form of the disease, type 4, is due to mutations in the SLC40A1 gene, which encodes for ferroportin (FPN). Hereditary hemochromatosis is commonly found in populations of European origin. By contrast, hemochromatosis in Asia is rare and less well understood and can be masked by the presence of iron deficiency and secondary iron overload from thalassemia. Here, we provide a comprehensive report of hemochromatosis in a group of patients of Asian origin. We have identified novel mutations in HJV, HAMP, and SLC40A1 in countries not normally associated with hereditary hemochromatosis (Pakistan, Bangladesh, Sri Lanka, and Thailand). Our family studies show a high degree of consanguinity, highlighting the increased risk of iron overload in many countries of the developing world and in countries in which there are large immigrant populations from these regions.

Original publication

DOI

10.1182/blood-2009-01-199109

Type

Journal article

Journal

Blood

Publication Date

02/07/2009

Volume

114

Pages

20 - 25

Keywords

Adolescent, Adult, Amino Acid Sequence, Antimicrobial Cationic Peptides, Asia, Asian Continental Ancestry Group, Cation Transport Proteins, Child, Consanguinity, Female, Genotype, Hemochromatosis, Hemochromatosis Protein, Hepcidins, Histocompatibility Antigens Class I, Humans, Iron Overload, Male, Membrane Proteins, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Phenotype, Sequence Homology, Amino Acid, Young Adult