Impaired metabolic function and signaling defects in phagocytic cells in glycogen storage disease type 1b.

Abstract

Patients with glycogen storage disease (GSD) type lb (lb), in contrast to patients with GSD type la (la), are susceptible to recurrent bacterial infections suggesting an impairment in their immune system. In this study, phagocytic cell (neutrophil and monocyte) respiratory burst activity, as measured by superoxide anion generation, oxygen consumption, and hexose monophosphate shunt activity, was markedly reduced in both neutrophils and monocytes from GSD lb patients as compared with either GSD la patients or healthy adult control cells. Degranulation, unlike respiratory burst activity, was not significantly different in neutrophils from GSD lb patients as compared with controls. Both neutrophils and monocytes from GSD lb patients showed decreased ability to elevate cytosolic calcium in response to the chemotactic peptide f-Met-LeuPhe. In addition, calcium mobilization in response to ionomycin was also attenuated suggesting decreased calcium stores.

Interferon-γ Corrects the Respiratory Burst Defect In Vitro in Monocyte-Derived Macrophages from Glycogen Storage Disease Type 1b Patients

“…This reduction in 02-production in GSD Ib MDM (42% of controls) was similar to the reduction in respiratory burst activity we reported in GSD I b monocyte suspensions (32% of controls, 11 = 3 patients) and neutrophils (1 7% of controls, 11 = 3 patients) (18,19). Defective generation of 01-was also observed in GSD with control short-term in vilro indicates that the defect is intrinsic and is not MDM cultured in the absence of IFN-y.…”

“…Multiple functional abnormalities have been identified including chemotaxis, bactericidal activity, respiratory burst activity, and glucose transport (12)(13)(14)(15)(16)(17)(18). We previously demonstrated that the defect in respiratory burst activity was associated with impaired calcium mobilization and decreased intracellular calcium stores (18,19).…”

In Vitro and In Vivo Effects of Granulocyte Colony-Stimulating Factor on Neutrophils in Glycogen Storage Disease Type IB: Granulocyte Colony-Stimulating Factor Therapy Corrects the Neutropenia and the Defects in Respiratory Burst Activity and Ca2+ Mobilization

“…(Pe-1 3-17). In previous studies, we have demonstrated decreased diatr Res 35: 84-90, 1994) 02-production associated with blunted Ca2+ mobilization in phagocytic cells from GSD 1 b patients (18,19). However, the Abbreviations specific phagocytic cell defect has yet to be identified.…”

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

“…Monocyte functions are also abnormal, probably contributing to the formation of granulomas and chronic inflammatory responses. 151 It is also important to note that some patients with GSD Ia have also been known to develop neutropenia. Individuals with GSD Ia who are homozygous for the mutation p.Gly188Arg were reported to have a GSD Ib-like phenotype with neutropenia.…”