2. Academic Validation
  3. Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin

Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin

  • Blood Cells Mol Dis. 2018 Mar;69:23-29. doi: 10.1016/j.bcmd.2017.04.003.
Renata Mojzikova 1,  Pavla Koralkova 2,  Dusan Holub 3,  Zuzana Saxova 4,  Dagmar Pospisilova 5,  Daniela Prochazkova 6,  Petr Dzubak 3,  Monika Horvathova 4,  Vladimir Divoky 4
Affiliations

Affiliations

  • 1 Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. Electronic address: r.mojzikova@gmail.com.
  • 2 Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
  • 3 Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
  • 4 Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
  • 5 Department of Pediatrics, University Hospital and Faculty of Medicine and Dentistry, Olomouc, Czech Republic.
  • 6 Department of Pediatrics, Masaryk Hospital in Usti nad Labem, Czech Republic.
PMID: 28803808 DOI: 10.1016/j.bcmd.2017.04.003
Abstract

Glucose-6-phosphate isomerase (GPI) deficiency, a genetic disorder responsible for chronic nonspherocytic hemolytic anemia, is the second most common red blood cell glycolytic enzymopathy. We report three patients from two unrelated families of Czech and Slovak origin with macrocytic hemolytic anemia due to GPI deficiency. The first patient had 15% of residual GPI activity resulting from two new heterozygous missense mutations c.478T>C and c.1414C>T leading to substitutions p.(Ser160Pro) and p.(Arg472Cys). Two Other patients (siblings) inherited the same c.1414C>T p.(Arg472Cys) mutation in a homozygous constitution and lost approximately 89% of their GPI activity. Erythroid hyperplasia with dysplastic features was observed in the bone marrow of all three patients. Low hepcidin/ferritin ratio and elevated soluble Transferrin Receptor detected in our GPI-deficient patients suggest disturbed balance between erythropoiesis and iron metabolism contributing to iron overload.

Keywords

Dysplastic erythropoiesis; Glucose-6-phosphate isomerase deficiency; Hemolytic anemia; Hepcidin to ferritin ratio; Iron loading; Soluble transferrin receptor.

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