Hereditary erythrocytosis, thrombocytosis and neutrophilia

Best Pract Res Clin Haematol. 2014 Jun;27(2):95-106. doi: 10.1016/j.beha.2014.07.002. Epub 2014 Jul 18.

Abstract

Hereditary erythrocytosis, thrombocytosis, and neutrophilia are rare inherited syndromes which exhibit Mendelian inheritance. Some patients with primary hereditary erythrocytosis exhibit a mutation in the erythropoietin receptor (EPOR) which is associated with low serum erythropoietin (EPO) levels. Secondary congenital erythrocytosis may be characterized by normal or high serum EPO levels, and is related to high oxygen affinity haemoglobin variants, mutation of the enzyme biphosphoglycerate mutase (BPGM), or defects in components of the oxygen-sensing pathway. Hereditary thrombocytosis was first linked to mutations in genes encoding thrombopoietin (THPO) or the thrombopoietin receptor, MPL. More recently, germline mutations in JAK2, distinct from JAK2 V617F, and mutation of the gelsolin gene, were uncovered in several pedigrees of hereditary thrombocytosis. Hereditary neutrophilia has been described in one family with an activating germline mutation in CSF3R. The mutational basis for most hereditary myeloproliferative disorders has yet to be identified.

Keywords: JAK2; MPL; TPO; familial; hereditary erythrocytosis; neutrophilia; polycythaemia; thrombocytosis.

Publication types

  • Review

MeSH terms

  • Bisphosphoglycerate Mutase / genetics
  • Bisphosphoglycerate Mutase / metabolism
  • Erythropoietin / genetics
  • Erythropoietin / metabolism
  • Gelsolin / genetics
  • Gelsolin / metabolism
  • Gene Expression
  • Hemoglobins / metabolism
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Leukocyte Disorders / congenital*
  • Leukocyte Disorders / diagnosis
  • Leukocyte Disorders / genetics
  • Leukocyte Disorders / metabolism
  • Leukocyte Disorders / pathology
  • Mutation*
  • Oxygen / metabolism
  • Polycythemia / congenital*
  • Polycythemia / diagnosis
  • Polycythemia / genetics
  • Polycythemia / metabolism
  • Polycythemia / pathology
  • Receptors, Colony-Stimulating Factor / genetics
  • Receptors, Colony-Stimulating Factor / metabolism
  • Receptors, Erythropoietin / genetics
  • Receptors, Erythropoietin / metabolism
  • Receptors, Thrombopoietin / genetics
  • Receptors, Thrombopoietin / metabolism
  • Signal Transduction
  • Thrombocytosis / diagnosis
  • Thrombocytosis / genetics*
  • Thrombocytosis / metabolism
  • Thrombocytosis / pathology
  • Thrombopoietin / genetics
  • Thrombopoietin / metabolism

Substances

  • CSF3R protein, human
  • EPO protein, human
  • Gelsolin
  • Hemoglobins
  • Receptors, Colony-Stimulating Factor
  • Receptors, Erythropoietin
  • Receptors, Thrombopoietin
  • Erythropoietin
  • MPL protein, human
  • Thrombopoietin
  • JAK2 protein, human
  • Janus Kinase 2
  • Bisphosphoglycerate Mutase
  • Oxygen

Supplementary concepts

  • Neutrophilia, Hereditary
  • Polycythemia, primary familial and congenital