Table 1 Summary of hereditary hemochromatosis classification, nomenclature, pathogenesis and major clinical features
From: EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)
Disease name | Synonyms | ORPHANET number | OMIM number | Chromosome position | Gene | Reference number | Pathogenesis | Major clinical features |
|---|---|---|---|---|---|---|---|---|
HFE- related hemochromatosis | Hemochromatosis type 1 p.C282Y/p.C282Y hemochromatosis Classic hemochromatosis | 139 489 | 235 200 | 6p22.2 | HFE | NM_000410.3 | Ineffective hepcidin-mediated ferroportin downregulation | Adult onset Autosomal recessive Increased TS and SF Liver iron overload |
Non-HFE-related hemochromatosis | Hemochromatosis type 2A Juvenile hemochromatosis | 79 230 | 602 390 | 1q21.1 | HJV | NM_213653.3 | Ineffective hepcidin-mediated ferroportin downregulation | Juvenile onset Autosomal recessive Increased TS and SF Iron in hepatocytes |
Hemochromatosis type 2B Juvenile hemochromatosis | 79 230 | 613 313 | 19q13.12 | HAMP | NM_021175.2 | Hepcidin defective synthesis | Juvenile onset Autosomal recessive Increased TS and SF Iron in hepatocytes | |
Hemochromatosis type 3 TFR2-related hemochromatosis | 225 123 | 604 250 | 7q22.1 | TFR2 | NM_003227.3 | Ineffective hepcidin-mediated ferroportin downregulation | Adult onset Autosomal recessive Increased TS and SF Iron in hepatocytes | |
Hemochromatosis type 4B Non-classical ferroportin disease with GOF mutations (type B) | 2q32.2 | SLC40A1 | NM_014585.5 | Ferroportin gain of function excessive ferroportin-mediated cellular iron export | Adult onset Autosomal dominant Increased TS and SF Iron in hepatocytes | |||
Ferroportin disease | Hemochromatosis type 4A Classical ferroportin disease with LOF mutations (type A) | 139 491 | 606 069 | 2q32.2 | SLC40A1 | NM_014585.5 | Ferroportin loss of functiondefective ferroportin-mediated cellular iron export | Adult onset Autosomal dominant Normal TS; increased SF Iron in Kupffer cells and macrophages (liver and spleen) |
