Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib
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Sarajlija, AdrijanĐorđević, Maja
Kecman, Bozica
Skakić, Anita
Pavlović, Sonja
Pasić, Srdjan
Stojiljković, Maja
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Background: 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. Methods: 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. Results: Absolute neutrophil count (ANC) lt 1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC lt 500/mm(3)) 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 gt A/c.785G gt A and c.81T gt A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G gt 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. Conclusions: 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.
Keywords:
Phenotype / Neutropenia / Glycogen storage disease type Ib / GenotypeSource:
European Journal of Medical Genetics, 2020, 63, 3Publisher:
- Elsevier, Amsterdam
Funding / projects:
- Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
- Strengthening the Research Potential of IMGGE through Reinforcement of Biomedical Science of Rare Diseases in Serbia - en route for innovation (EU-FP7-316088)
DOI: 10.1016/j.ejmg.2019.103767
ISSN: 1769-7212
PubMed: 31536830
WoS: 000516852000015
Scopus: 2-s2.0-85072197353
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Sarajlija, Adrijan AU - Đorđević, Maja AU - Kecman, Bozica AU - Skakić, Anita AU - Pavlović, Sonja AU - Pasić, Srdjan AU - Stojiljković, Maja PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1387 AB - Background: 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. Methods: 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. Results: Absolute neutrophil count (ANC) lt 1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC lt 500/mm(3)) 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 gt A/c.785G gt A and c.81T gt A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G gt 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. Conclusions: 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. PB - Elsevier, Amsterdam T2 - European Journal of Medical Genetics T1 - Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib IS - 3 VL - 63 DO - 10.1016/j.ejmg.2019.103767 ER -
@article{ author = "Sarajlija, Adrijan and Đorđević, Maja and Kecman, Bozica and Skakić, Anita and Pavlović, Sonja and Pasić, Srdjan and Stojiljković, Maja", year = "2020", abstract = "Background: 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. Methods: 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. Results: Absolute neutrophil count (ANC) lt 1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC lt 500/mm(3)) 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 gt A/c.785G gt A and c.81T gt A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G gt 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. Conclusions: 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.", publisher = "Elsevier, Amsterdam", journal = "European Journal of Medical Genetics", title = "Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib", number = "3", volume = "63", doi = "10.1016/j.ejmg.2019.103767" }
Sarajlija, A., Đorđević, M., Kecman, B., Skakić, A., Pavlović, S., Pasić, S.,& Stojiljković, M.. (2020). Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib. in European Journal of Medical Genetics Elsevier, Amsterdam., 63(3). https://doi.org/10.1016/j.ejmg.2019.103767
Sarajlija A, Đorđević M, Kecman B, Skakić A, Pavlović S, Pasić S, Stojiljković M. Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib. in European Journal of Medical Genetics. 2020;63(3). doi:10.1016/j.ejmg.2019.103767 .
Sarajlija, Adrijan, Đorđević, Maja, Kecman, Bozica, Skakić, Anita, Pavlović, Sonja, Pasić, Srdjan, Stojiljković, Maja, "Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib" in European Journal of Medical Genetics, 63, no. 3 (2020), https://doi.org/10.1016/j.ejmg.2019.103767 . .