Melis D 1 , Carbone F 2 , Della Casa R 1 , Minopoli G 1 , Parenti G 1 , Andria G 1 , Matarese G 2 1 Dept Pediatrics, Federico II University, Naples, Italy 2 Lab. Immunologia IEOS-CNR, Naples, Italy Background: Glycogen storage disease type 1b (GSD1b) is caused by mutations in the glucose 6-phosphate translocase (G6PT) gene. GSD1b patients present autoimmune disorders including inflammatory bowel disease (IBD), thyroid disease and Myastenia Gravis. Although these manifestations impact significantly on patients' quality of life, their pathophysiology has remained obscure. Patients and methods: Seven GSD1b and 14 age and sex-matched controls were enrolled. The presence of autoimmune disorders, serum levels of different autoantibodies, classes and subclasses of circulating lymphocytes, T cells activity in vitro, activity and number of T-cellsregulating system (TRegs) were investigated. Results: The CD3, CD4, CD8, NK, CD4CD28, CD3CD45RA, CD3CD45RO, CD4CD45RO lymphocytes counts were lower in patients than in controls. Aweak proliferation activity was observed in both homologous and heterologous sera. The patients also showed reduced TReg cells counts in the periphery. The presence of autoimmune thyroid disease correlated with CD8DR cells prevalence. The diagnosis of IBD inversely correlated with NK and CD4CD8 cells prevalence. The serum levels of acetylcholine receptor antibodies inversely correlated with CD4CD8, CD4CD45RA cells prevalence. Conclusion: The obtained data suggest that the association of lymphopenia, impaired T cell proliferation and reduced TReg cells is responsible for the development of autoimmune disorders in GSD1b patients.