Pathogenesis, Diagnostics, and Treatment of Hereditary Haemochromatosis: A 150 Year-Long Understanding of an Iron Overload Disorder

Abstract

Haemochromatosis is an iron overload disorder that can be inherited or acquired and when diagnosis is delayed, disease progression and death can occur. Iron overload was first described by the French internist Armand Trousseau in 1865 in an article on diabetes in which alterations in skin pigmentations were reported. Some years later, the German pathologist Friedrich Daniel von Recklinghausen coined the term ‘haemochromatosis’ for a metabolic disorder characterised by excess deposition of iron in the tissue. This disorder affects 1 in 200 subjects of Caucasians of Northern European descent. The systemic excess iron build-up condition quickly gained an intense clinical interest. Haemochromatosis can lead to severe pathological symptoms in multiple organs, including the liver, bones, spleen, heart, pancreas, joints, and reproductive organs. With the progress of the disease, hepatic damage predominates. Polymorphisms in several independent genes can lead to haemochromatosis. However, the most widely known haemochromatosis-associated and studied ones are genetic variants in the HFE gene, located on the short arm of human chromosome 6. Early detection and phlebotomy prior to the onset of fibrosis/cirrhosis can reduce morbidity and normalise life expectancy. Consequently, phlebotomy has been accepted for decades as a standard treatment for the reduction of iron load. Nowadays, other methods, such as erythrocytapheresis, therapeutic application of iron chelators and proton pump inhibitors, or hepcidin-targeted therapy, are discussed as alternative personalised treatments of hereditary haemochromatosis. This review focusses on the pathogenesis, diagnosis, and therapy of haemochromatosis.