Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.
Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration.
Department of Internal Medicine, division of Endocrinology and Metabolism, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: m.regenboog@amc.uva.nl.
Martine
M
Regenboog
Laboratory Genetic Metabolic Diseases, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: a.b.vankuilenburg@amc.uva.nl.
André B P
AB
van Kuilenburg
Department of Pathology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.verheij@amc.uva.nl.
Joanne
J
Verheij
Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: dorine.swinkels@radboudumc.nl.
Dorine W
DW
Swinkels
Department of Internal Medicine, division of Endocrinology and Metabolism, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: c.e.hollak@amc.uva.nl.
Carla E M
CE
Hollak
D005293:Ferritins / Q000097:blood / Q000378:metabolism*; D005776:Gaucher Disease / Q000150:complications / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D064451:Hepcidins / Q000097:blood / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000209:etiology / Q000628:therapy; D024821:Metabolic Syndrome / Q000209:etiology / Q000628:therapy; D009369:Neoplasms / Q000209:etiology; D019636:Neurodegenerative Diseases / Q000209:etiology
D064451:Hepcidins; D005293:Ferritins; D007501:Iron
Carcinogenesis; Ferritin; Gaucher disease; Hepcidin; Iron metabolism