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
20 - Divalent metal transporter-1 (SLC11A2) iron overload
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
Divalent metal transporter-1 (DMT1) is a member of the “natural-resistance-associated macrophage protein” (Nramp) family. DMT1 is upregulated by dietary iron deficiency, is expressed strongly on the microvillus membranes of duodenal enterocytes at the villus tips, and is a key mediator of iron absorption. DMT1 also mediates iron transfer from endosomes into the cytosol of developing erythroid cells. The SLC11A2 gene that encodes DMT1 is located on chromosome 12q13 (OMIM *604653).
In 1964, Shahidi and colleagues described a brother and sister of French-Canadian descent who had hypochromic, microcytic anemia. These siblings also had elevated serum iron concentrations, massive deposition of iron in hepatocytes, and absence of stainable iron in the bone marrow. These children apparently had no defect in transferrin or heme synthesis. Two of their siblings appeared to have normal iron phenotypes. In 2004 and 2005, Priwitzerova and colleagues described a Czech female in a consanguineous kinship who came to medical attention at age 3 months because she had a syndrome of abnormal iron metabolism characterized by severe hypochromic, microcytic anemia, erythroid hyperplasia, abnormal erythroid maturation, elevated serum iron concentration, normal to slightly increased serum ferritin level, and markedly increased serum transferrin receptor levels. In 2005, Mims and colleagues reported that this woman was homozygous for a mutation in SLC11A2.
Clinical description
Clinical observations in patients with two SLC11A2 mutations are limited. In one case, left ventricular hypertrophy was detected before birth, and birth weight was low. Pallor is presumed to have been present in all reported cases.
- Type
- Chapter
- Information
- Handbook of Iron Overload Disorders , pp. 228 - 232Publisher: Cambridge University PressPrint publication year: 2010