Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2)

Achille Iolascon, Maria D'Apolito, Veronica Servedio, Flora Cimmino, Antonio Piga, Clara Camaschella

Research output: Contribution to journalArticle

Abstract

Divalent metal transporter 1 (DMT1) mediates apical iron uptake in duodenal enterocytes and iron transfer from the transferrin receptor endosomal cycle into the cytosol in erythroid cells. Both mk mice and Belgrade rats, which carry an identical DMT1 mutation, exhibit severe microcytic anemia at birth and defective intestinal iron use and erythroid iron use. We report the hematologic phenotype of a child, compound heterozygote for 2 DMT1 mutations, who was affected by severe anemia since birth and showed hepatic iron overload. The novel mutations were a 3-bp deletion in intron 4 (c.310-3_5del CTT) resulting in a splicing abnormality and a C>T transition at nucleotide 1246(p. R416C). A striking reduction of DMT1 protein in peripheral blood mononuclear cells was demonstrated by Western blot analysis. The proband required blood transfusions until erythropoietin treatment allowed transfusion independence when hemoglobin levels between 75 and 95 g/L (7.5 and 9.5 g/dL) were achieved. Hematologic data of this patient at birth and in the first years of life strengthen the essential role of DMT1 in erythropoiesis. The early onset of iron overload indicates that, as in animal models, DMT1 is dispensable for liver iron uptake, whereas its deficiency in the gut is likely bypassed by the up-regulation of other pathways of iron use.

Original languageEnglish
Pages (from-to)349-354
Number of pages6
JournalBlood
Volume107
Issue number1
DOIs
Publication statusPublished - Jan 1 2006

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2)'. Together they form a unique fingerprint.

  • Cite this

    Iolascon, A., D'Apolito, M., Servedio, V., Cimmino, F., Piga, A., & Camaschella, C. (2006). Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood, 107(1), 349-354. https://doi.org/10.1182/blood-2005-06-2477