Book contents
- Frontmatter
- Contents
- Foreword by Anthony S. Tavill
- Preface
- 1 History of iron overload disorders
- 2 Normal iron absorption and metabolism
- 3 Iron toxicity
- 4 Tests for hemochromatosis and iron overload
- 5 Complications of hemochromatosis and iron overload
- 6 Insulin resistance and iron overload
- 7 Infections and immunity
- 8 Classical and atypical HFE hemochromatosis
- 9 Heterozygosity for HFE C282Y
- 10 Porphyria cutanea tarda
- 11 Mitochondrial mutations as modifiers of hemochromatosis
- 12 Hemochromatosis associated with ferroportin gene (SLC40A1) mutations
- 13 Hemochromatosis associated with hemojuvelin gene (HJV) mutations
- 14 Hemochromatosis associated with hepcidin gene (HAMP) mutations
- 15 Hemochromatosis associated with transferrin receptor-2 gene (TFR2) mutations
- 16 Iron overload associated with IRE mutation of ferritin heavy-chain gene (FTH1)
- 17 Hereditary hyperferritinemia-cataract syndrome: IRE mutations of ferritin light-chain gene (FTL)
- 18 Iron overload in Native Africans and African-Americans
- 19 Hereditary atransferrinemia
- 20 Divalent metal transporter-1 (SLC11A2) iron overload
- 21 Iron overload associated with thalassemia syndromes
- 22 Iron overload associated with hemoglobinopathies
- 23 Iron overload associated with pyruvate kinase deficiency
- 24 Iron overload associated with congenital dyserythropoietic anemias
- 25 Hereditary sideroblastic anemias
- 26 Pearson marrow–pancreas syndrome
- 27 Acquired sideroblastic anemias
- 28 Hereditary aceruloplasminemia
- 29 Friedreich ataxia and cardiomyopathy
- 30 Pantothenate kinase (PANK2)-associated neurodegeneration
- 31 Neuroferritinopathies
- 32 GRACILE syndrome
- 33 Neonatal hemochromatosis
- 34 Iron overload due to excessive supplementation
- 35 Localized iron overload
- 36 Management of iron overload
- 37 Population screening for hemochromatosis
- 38 Ethical, legal, and social implications
- 39 Directions for future research
- Index
- Plate section
- References
15 - Hemochromatosis associated with transferrin receptor-2 gene (TFR2) mutations
Published online by Cambridge University Press: 01 June 2011
- Frontmatter
- Contents
- Foreword by Anthony S. Tavill
- Preface
- 1 History of iron overload disorders
- 2 Normal iron absorption and metabolism
- 3 Iron toxicity
- 4 Tests for hemochromatosis and iron overload
- 5 Complications of hemochromatosis and iron overload
- 6 Insulin resistance and iron overload
- 7 Infections and immunity
- 8 Classical and atypical HFE hemochromatosis
- 9 Heterozygosity for HFE C282Y
- 10 Porphyria cutanea tarda
- 11 Mitochondrial mutations as modifiers of hemochromatosis
- 12 Hemochromatosis associated with ferroportin gene (SLC40A1) mutations
- 13 Hemochromatosis associated with hemojuvelin gene (HJV) mutations
- 14 Hemochromatosis associated with hepcidin gene (HAMP) mutations
- 15 Hemochromatosis associated with transferrin receptor-2 gene (TFR2) mutations
- 16 Iron overload associated with IRE mutation of ferritin heavy-chain gene (FTH1)
- 17 Hereditary hyperferritinemia-cataract syndrome: IRE mutations of ferritin light-chain gene (FTL)
- 18 Iron overload in Native Africans and African-Americans
- 19 Hereditary atransferrinemia
- 20 Divalent metal transporter-1 (SLC11A2) iron overload
- 21 Iron overload associated with thalassemia syndromes
- 22 Iron overload associated with hemoglobinopathies
- 23 Iron overload associated with pyruvate kinase deficiency
- 24 Iron overload associated with congenital dyserythropoietic anemias
- 25 Hereditary sideroblastic anemias
- 26 Pearson marrow–pancreas syndrome
- 27 Acquired sideroblastic anemias
- 28 Hereditary aceruloplasminemia
- 29 Friedreich ataxia and cardiomyopathy
- 30 Pantothenate kinase (PANK2)-associated neurodegeneration
- 31 Neuroferritinopathies
- 32 GRACILE syndrome
- 33 Neonatal hemochromatosis
- 34 Iron overload due to excessive supplementation
- 35 Localized iron overload
- 36 Management of iron overload
- 37 Population screening for hemochromatosis
- 38 Ethical, legal, and social implications
- 39 Directions for future research
- Index
- Plate section
- References
Summary
TFR2 hemochromatosis (OMIM #604250) is a rare autosomal recessive disorder characterized by elevated serum iron measures, parenchymal iron deposition, and complications of iron overload. In some kinships, severe iron overload occurs in children or young adults. In individual cases, the TFR2 hemochromatosis phenotype may resemble that of HFE hemochromatosis or HJVhemochromatosis (Chapter 8).
History
In 1999, Kawabata and colleagues cloned and sequenced a human gene homologous to the TFR gene that encodes classical transferrin receptor (TFR1). They named the newly discovered gene TFR2 (OMIM *604720), and mapped it to chromosome 7q22. Two transcripts (alpha and beta) are expressed from this gene; the alpha transcript is expressed predominantly in the liver. TFR2-alpha is a second transferrin receptor that mediates cellular iron transport in vitro. In normal subjects, most iron uptake by the liver is transferrin mediated. Expression of TFR1 in hepatocytes, as in other non-reticuloendothelial cell types, is down-regulated in response to increased intracellular iron. Consequently, hepatocyte TFR1 is undetectable in patients with HFE hemochromatosis and hepatic iron loading. Nonetheless, hepatic iron loading in HFE hemochromatosis is progressive. Experiments in mice demonstrate that TFR2 makes only a minor contribution to the uptake of transferrin-bound iron by the liver, but rather TFR2 is thought to modulate the signaling pathway that controls hepcidin expression. In 2000, Camaschella and colleagues described persons with hemochromatosis phenotypes in two unrelated Sicilian families who had mutations in TFR2.
Clinical characteristics
The age of onset and severity of iron overload varies moderately in patients with TFR2 hemochromatosis.
- Type
- Chapter
- Information
- Handbook of Iron Overload Disorders , pp. 193 - 199Publisher: Cambridge University PressPrint publication year: 2010