Two Cases of 22Q11.2 Deletion Syndrome and Type 1 Diabetes

ABSTRACT Objective: 22q11.2 Deletion syndrome (22q11.2DS) is the most common chromosome deletion syndrome and increases the risk of autoimmune conditions, including thyroid disease, cytopenias, and juvenile rheumatoid arthritis. We report two unusual cases of pediatric patients with 22q11.2DS who subsequently developed type 1 diabetes (T1D). Methods: Clinical and laboratory data were isolated and are presented. Results: A 7-year-old male with genetically confirmed 22q11.2DS and related characteristics presented with polyuria, nocturia, and polydipsia and was found to have an elevated hemoglobin A1c of 9.8% (84 mmol/mol) with subsequent positive pancreatic autoantibodies (islet antigen 2 [IA-2] antibody and glutamic acid decarboxylase antibody). Screening labs for other autoimmune conditions identified thyroid antibodies, but thyroid function has been normal thus far. A 4-year-old female with genetically confirmed 22q11.2DS and associated features presented in severe diabetic ketoacidosis and was found to have one positive pancreatic autoantibody (IA-2), confirming T1D. Screening labs for associated autoimmune conditions revealed negative 21-hydroxylase antibodies, mildly elevated thyroid-stimulating hormone with normal free thyroxine and negative celiac screen. Conclusion: Despite the increased prevalence of autoimmune conditions in 22q11.2DS, the relationship with T1D is unknown. Studies have identified an increased prevalence of pancreatic autoantibodies in patients with 22q11.2DS, yet conversion to T1D is rare. This raises the question of a potential protective mechanism versus underrecognition. Abbreviations: 22q11.2DS 22q11.2 deletion syndrome FISH fluorescence in situ hybridization GAD65 glutamic acid decarboxylase HbA1c glycated hemoglobin IA-2 islet antigen 2 T1D type 1 diabetes