Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease

被引:47
作者
Zoller, H
McFarlane, I
Theurl, I
Stadlmann, S
Nemeth, E
Oxley, D
Ganz, T
Halsall, DJ
Cox, TM
Vogel, W
机构
[1] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England
[2] Innsbruck Med Univ, Clin Div Gastroenterol & Hepatol, Innsbruck, Austria
[3] Innsbruck Med Univ, Clin Div Gen Internal Med, Innsbruck, Austria
[4] Cambridge Univ Hosp NHS Trust, Dept Clin Biochem, Cambridge, England
[5] Innsbruck Med Univ, Dept Pathol, Innsbruck, Austria
[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA
[7] Babraham Inst, Cambridge, England
基金
英国惠康基金;
关键词
D O I
10.1002/hep.20775
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of human iron metabolism, characterized by iron deposition in macrophages, including Kupfer cells. Mutations in the gene encoding ferroportin 1, a cellular iron exporter, are responsible for this iron storage disease, inherited as an autosomal dominant trait. We present clinical, histopathological, and radiological findings in a family with the most common ferroportin mutation, V162del. In the index case, the disorder is characterized by abundant deposition of hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric and duodenal mucosa, and also in squamous cell carcinoma of the lung). The radiological findings indicated the presence of excess iron in bone marrow and spleen. Despite a significant burden of iron, no features of chronic liver disease were found in affected members of the family, including individuals aged up to 80 years. Hyperferritinemia greater than 1,000 mu g/L was a penetrant biochemical finding before the second decade in life and was associated with significantly increased serum concentrations of pro-hepcidin that correlated positively with urinary hepcidin concentrations. In conclusion, the systemic iron burden in ferroportin disease is not a sufficient cause for chronic liver disease. In patients with most, but not all, ferroportin mutations, retention of iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. Finally, macrophage iron storage in ferroportin disease is associated with elevated serum pro-hepcidin levels.
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收藏
页码:466 / 472
页数:7
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