G6PC3 mutations cause non-syndromic severe congenital neutropenia

Mol Genet Metab. 2013 Feb;108(2):138-41. doi: 10.1016/j.ymgme.2012.12.001. Epub 2012 Dec 21.


The deficiency of ubiquitously expressed glucose-6-phosphatase (G6PC3) enzyme is known to result in a syndrome characterized by severe congenital neutropenia, prominent superficial venous pattern, congenital heart defects and genito-urinary malformations. Here, we describe four patients from three families with non-syndromic severe congenital neutropenia and identify four G6PC3 mutations as causative in these cases. Thus we demonstrate that G6PC3 mutations also result in a non-syndromic form of severe congenital neutropenia. We propose that G6PC3 deficiency should be considered as part of the differential diagnoses in any patient with unexplained congenital neutropenia. Additionally, we show a relationship between the genotype and non-hematological phenotype of G6PC3 deficiency. These findings may provide an insight into the role of the G6PC3 enzyme and glucose metabolism in developmental pathways.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • Congenital Bone Marrow Failure Syndromes
  • Exons
  • Female
  • Genotype
  • Glucose-6-Phosphatase / genetics*
  • Humans
  • Mutation*
  • Neutropenia / congenital*
  • Neutropenia / genetics
  • Sequence Alignment


  • Glucose-6-Phosphatase
  • G6PC3 protein, human

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3