Hemochromatosis classification: update and recommendations by the BIOIRON Society

Hemochromatosis (HC) is a genetically heterogeneous disorder in which uncontrolled intestinal iron absorption may lead to progressive iron overload (IO) responsible for disabling and life-threatening complications such as arthritis, diabetes, heart failure, hepatic cirrhosis, and hepatocellular carcinoma. The recent advances in the knowledge of pathophysiology and molecular basis of iron metabolism have highlighted that HC is caused by mutations in at least 5 genes, resulting in insufficient hepcidin production or, rarely, resistance to hepcidin action. This has led to an HC classification based on different molecular subtypes, mainly reflecting successive gene discovery. This scheme was difficult to adopt in clinical practice and therefore needs revision. Here we present recommendations for unambiguous HC classifi-cation developed by a working group of the Interna-tional Society for the Study of Iron in Biology and Medicine (BIOIRON Society), including both clinicians and basic scientists during a meeting in Heidelberg, Ger-many. We propose to deemphasize the use of the molec-ular subtype criteria in favor of a classification addressing both clinical issues and molecular complexity. Ferroportin disease (former type 4a) has been excluded because of its distinct phenotype. The novel classifica-tion aims to be of practical help whenever a detailed molecular characterization of HC is not readily available.

Automated summary

Hemochromatosis is a genetically heterogenous disorder characterized by uncontrolled intestinal iron absorption leading to iron overload and potentially life-threatening complications. Recent research has identified mutations in at least 5 genes as the main cause of the disease, affecting hepcidin production or action.