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Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib.

Authors
  • Sarajlija, Adrijan1
  • Djordjevic, Maja2
  • Kecman, Bozica3
  • Skakic, Anita4
  • Pavlovic, Sonja4
  • Pasic, Srdjan5
  • Stojiljkovic, Maja4
  • 1 Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic", Department of Metabolism and Clinical Genetics, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: [email protected] , (Serbia)
  • 2 Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic", Department of Metabolism and Clinical Genetics, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. , (Serbia)
  • 3 Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic", Department of Metabolism and Clinical Genetics, Belgrade, Serbia. , (Serbia)
  • 4 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. , (Serbia)
  • 5 Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic", Department of Immunology, Belgrade, Serbia. , (Serbia)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Mar 01, 2020
Volume
63
Issue
3
Pages
103767–103767
Identifiers
DOI: 10.1016/j.ejmg.2019.103767
PMID: 31536830
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. Absolute neutrophil count (ANC) < 1500/mm3 was present in all 33 patients, with severe neutropenia (ANC<500/mm3) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T>A/c.785G>A and c.81T>A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G>A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI. Copyright © 2019 Elsevier Masson SAS. All rights reserved.

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