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

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) < 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. 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.