Haemochromatosis in the new millennium

Powell, Lawrie W., Subramaniam, V. Nathan and Yapp, Thomas R. (2000) Haemochromatosis in the new millennium. Journal of Hepatology, 32 Supplement 1: 48-62. doi:10.1016/S0168-8278(00)80415-8

Author Powell, Lawrie W.
Subramaniam, V. Nathan
Yapp, Thomas R.
Title Haemochromatosis in the new millennium
Journal name Journal of Hepatology   Check publisher's open access policy
ISSN 0168-8278
Publication date 2000-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/S0168-8278(00)80415-8
Volume 32
Issue Supplement 1
Start page 48
End page 62
Total pages 15
Editor J. Rodes
Place of publication Amsterdam
Publisher Munksgaard International
Collection year 2000
Language eng
Subject C1
321008 Haematology
321202 Epidemiology
730103 Blood disorders
Abstract Hereditary haemochromatosis (HHC) is a common inherited disorder of iron metabolism characterised by progressive iron loading of parenchymal cells of the liver, pancreas, heart and other organs ultimately leading to cirrhosis and organ failure, Despite HLA studies which localised the defective gene to the short arm of chromosome 6, the haemochromatosis gene remained elusive until 1996, when the gene was identified by a massive positional cloning effort. The haemochromatosis gene (HFE) encodes a novel nonclassical MHC class-1-like molecule, Two missense mutations have been identified in patients with HHC, a G to A at nucleotide 845, resulting in a substitution of tyrosine for cysteine at amino acid 282 (referred to as the C282Y mutation) and a C to G at nucleotide 187, resulting in a substitution of aspartate for histidine at amino acid 63 (H63D). An average of 85-90% of patients with typical clinical features of HHC are homozygous for the C282Y mutation. H63D is not associated with the same degree of iron loading as C282Y, Clinical expression is variable depending on environmental (dietary) iron, physiological and pathological blood loss and as yet unidentified modifying genetic factors. One recent Australian study indicates that only about 50% of homozygous subjects are fully expressing and symptomatic and that about 30% show no clinical or biochemical expression. Genetic tests for identifying mutations in the HFE gene provide precise means for diagnosis, family testing and population screening and have led to re-evaluation of the indications for liver biopsy in this, disease. At the present time, however, the most practical and cost-effective method of screening is for phenotypic expression by transferrin saturation or unsaturated iron binding capacity measurement. In the future, population screening by genotype should be feasible once the relevant technical, legal and ethical issues are resolved.
Keyword Gastroenterology & Hepatology
Iron Overload
Population Screening
Major Histocompatibility Complex
Hepatic Transferrin Receptor
Hereditary Hemochromatosis
Genetic Hemochromatosis
Idiopathic Hemochromatosis
Australian Population
Perinatal Hemochromatosis
Q-Index Code C1

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
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Created: Tue, 10 Jun 2008, 10:41:50 EST