Abstract
Purpose
G6PC3 deficiency presents as a complex and heterogeneous syndrome that classically associates severe congenital neutropenia with cardiac and urogenital developmental defects. Here we investigate the findings of T cell lymphopenia and inflammatory bowel disease in a child with G6PC3 deficiency due to compound heterozygous mutations in intron 3 (c.IVS3-1 G>A) and exon 6 (c.G778G/C; p.Gly260/Arg).
Methods
Histological examination was conducted on all biopsy specimens. Immunophenotyping and lymphocyte proliferation assays were performed. Immunoglobulin levels and vaccine responses were measured.
Results
The patient showed persistent global T cell lymphopenia, with only 8 to 13 % of thymic naive CD31+CD45RA+ cells among CD4 T cells (normal range 27–60 %). Proliferation assays and vaccine responses were within normal limits. The gastrointestinal inflammatory lesions were very closely related to those of glycogen storage disease type 1b, with a Crohn’s-like appearance but without granuloma or increased cryptic abscesses. The gastrointestinal disease responded to infliximab therapy. These findings were associated with a polyclonal hypergammaglobuliemia G.
Conclusion
G6PC3 deficiency may present with inflammatory bowel disease and T cell lymphopenia. The diagnosis should thus be considered in a patient with chronic congenital neutropenia and gastrointestinal symptoms. Patients with confirmed disease should also undergo T cell phenotyping to rule out cellular immunodeficiency.
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Bégin, P., Patey, N., Mueller, P. et al. Inflammatory Bowel Disease and T cell Lymphopenia in G6PC3 Deficiency. J Clin Immunol 33, 520–525 (2013). https://doi.org/10.1007/s10875-012-9833-6
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DOI: https://doi.org/10.1007/s10875-012-9833-6