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Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whether the neutropenia is solely due to enhanced apoptosis of mature neutrophils or whether aberrant neutrophil development may also contribute. Here we demonstrate that hematopoietic progenitors from GSD-1b patients are not impaired in their capacity to develop into mature neutrophils. However, optimal survival of neutrophil progenitors from GSD-1b patients requires high glucose levels (> 200 mg dl−1), suggesting that even under normoglycemic conditions these cells are more prone to apoptosis. Furthermore, analysis of cytokine levels in peripheral blood suggests an inflammatory state with an inverse correlation between the level of inflammation and the number of neutrophils. Finally, in some patients, with low numbers of peripheral blood neutrophils, high numbers of neutrophils were observed in the intestine. Together, these results suggest that the neutropenia observed in GSD-1b patients is not caused by impaired maturation, but may be caused by both increased levels of apoptosis and egress of neutrophils from the blood to the inflamed tissues.

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Acknowledgements

M.B. was supported by ZonMW (Veni 916.76.137).

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Authors and Affiliations

  1. Department of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

    Gepke Visser

  2. Department of Pediatrics, Centre for Cellular and Molecular Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    Wilco de Jager & Berent J. Prakken

  3. Department of Cell Biology, University Medical Center, Utrecht, The Netherlands

    Liesbeth P. Verhagen & Paul J. Coffer

  4. Department of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, The Netherlands

    G. Peter A. Smit

  5. Division of Metabolic Diseases, Department of Pediatrics, Academic Medical Center (AMC), Amsterdam, The Netherlands

    Frits A. Wijburg

  6. Center of Molecular and Cellular Intervention, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands

    Paul J. Coffer

  7. Department of Hematology, Erasmus MC, Rotterdam, Dr. Molewaterplein 50, Faculty building Office Ee1330F, 3015, GE Rotterdam, The Netherlands

    Miranda Buitenhuis

  8. Erasmus MC Stem Cell Institute for Regenerative Medicine, Erasmus MC, Rotterdam, The Netherlands

    Miranda Buitenhuis

Authors
  1. Gepke Visser
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  2. Wilco de Jager
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  3. Liesbeth P. Verhagen
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  4. G. Peter A. Smit
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  5. Frits A. Wijburg
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  6. Berent J. Prakken
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  7. Paul J. Coffer
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  8. Miranda Buitenhuis
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Corresponding author

Correspondence to Miranda Buitenhuis.

Additional information

Communicated by: Alberto B. Burlina

Competing interest: None declared.

Gepke Visser, Wilco de Jager, contributed equally.

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Visser, G., de Jager, W., Verhagen, L.P. et al. Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients. J Inherit Metab Dis 35, 287–300 (2012). https://doi.org/10.1007/s10545-011-9379-4

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  • DOI: https://doi.org/10.1007/s10545-011-9379-4

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