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Hemochromatosis a Liver Disorder

12 February 2008

Hereditary disorder traceable to genetic defect in liver cells — Heidelberg scientists publish findings in "Cell Metabolism"

Hemochromatosis is a disorder of the liver and not of the duodenum, as previously supposed. Scientists from the Heidelberg University Hospital and the European Molecular Biology Laboratory (EMBL) have demonstrated in an animal model that a defective gene in the liver is responsible for the hereditary disorder. The genetic deficiency reduces the production of the hepcidin hormone that inhibits the uptake of iron in the duodenum. These findings represent a basis for new therapy approaches and have been published in the latest issue of the Cell Metabolism journal.

Hemochromatosis is one of the most frequent hereditary metabolic disorders in northern Europe. In Germany alone the estimated number of people affected by it is anything up to 100,000 at present. Iron is a vital component for the red blood cells, but a surplus of iron is dangerous.

In hemochromatosis there is an increased uptake in the duodenum of iron from food. The body cannot get rid of surplus iron, so it is deposited both in organs like the liver, the pancreas and the heart and also in the joints, thus impairing their normal functions. Liver cancer, diabetes mellitus, myocardial insufficiency and disorders of the joints are the result. The insidious disease affects men between the ages of 20 and 40. In women it frequently occurs after menopause when iron requirement is normally higher. So far, the only therapy has been bloodletting.

The genetic defect has long been identified, but not the mechanism

The genetic cause of the disorder is well-known: the HFE gene on chromosome 6, discovered back in 1996. "We knew that hemochromatosis occurs when there’s something wrong with HFE,” says Professor Dr. Martina Muckenthaler, head of molecular medicine, Department of Pediatric Oncology, Haematology, Immunology and Pulmonology at the Center for Pediatric and Adolescent Medicine, University of Heidelberg. "What we didn’t know was the organ or tissue in which HFE has to be active in order to prevent iron overload.”

Accordingly, the Heidelberg research groups headed by Professor Muckenthaler, Professor Dr. Wolfgang Stremmel, medical director of the Department of Gastroenterology, Hepatology and Infectious Diseases at Heidelberg University Hospital, and Professor Dr. Mathias Hentze, associate director of EMBL, bred mice lacking the HFE gene in different tissues.

The liver is the weak point, not the duodenum

It transpired that the only mice to display all symptoms of the disorder were those without the critical gene in the liver cells. "For a long time scientists assumed that hemochromatosis was an intestinal disorder because that’s where the uptake of iron takes place,” says Professor Hentze. "But our research proves that the liver is the weak point.”

The HFE gene contains the instructions for forming the protein that the liver cells use to establish whether the body has taken up sufficient iron. Then the liver cells produce a special hormone called hepdicin that enters the bloodstream and inhibits iron uptake in the duodenum. "HFE encourages the formation of hepdicin via a whole range of intermediate stages,” explains Professor Muckenthaler. "If this gene is defective, too little hepdicin is produced. Iron uptake cannot be inhibited and the result is an overload.”

Successful cooperation at the Molecular Medicine Partnership Unit (MMPU)

Since 2002 the Heidelberg University Hospital and the European Molecular Biology Laboratory (EMBL) have been collaborating successfully in the framework of the Molecular Medicine Partnership Unit (MMPU). The aim of MMPU is to combine basic molecular biology research with clinical medicine and thus achieve a deeper understanding of various diseases. Disorders of iron metabolism are a central concern.

More information on the internet at
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Vujic Spasic M, Kiss J, Herrmann T, Galy B, Martinache S, Stolte J, Gröne HJ, Stremmel W, Hentze MW, Muckenthaler MU: Hfe acts in hepatocytes to prevent hemochromatosis. Cell Metab. 2008 Feb;7(2):173-8.

(The original article can be requested from the Press Office of Heidelberg University Hospital at

Please address any inquiries to
Professor Dr. Martina Muckenthaler
Zentrum für Kinder und Jugendmedizin
Universitätsklinikum Heidelberg
phone: 06221/566923

Professor Dr. Matthias Hentze
Associate Director
EMBL Heidelberg
phone: 06221/3878501

Professor Dr. Wolfgang Stremmel
Ärztlicher Direktor der Abteilung Gastroenterologie, Hepatologie,
Infektionskrankheiten und Vergiftungen
Medizinische Universitätsklinik Heidelberg
phone: 06221/568705 (secretary)

For journalists’ inquiries
Dr. Annette Tuffs
Press and Public Relations Officer
Heidelberg University Hospital
Medical Faculty of the University of Heidelberg
Im Neuenheimer Feld 672
phone: 06221/564536
fax: 06221/564544

Dr. Michael Schwarz
Public Information Officer
University of Heidelberg
Editor: Email
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