New-Onset Type 1 Diabetes Mellitus (T1DM) in a Pediatric Patient with Beckwith-Wiedemann Syndrome

Abstract

Abstract Introduction Beckwith-Wiedemann Syndrome (BWS) is the most common overgrowth syndrome with up to 50% of infants found to have hypoglycemia which has been believed to be related to hyperinsulinemia. However, our case report highlights a patient with the unusual presentation of concurrent BWS and T1DM along with the discussion of genetic factors that may contribute to the pathogenesis. Clinical Case We present the case of a 4-year-old African American female with a past medical history of BWS, twin gestation, prematurity, omphalocele, and patent ductus arteriosus. Her BWS had been diagnosed at birth via genetic testing which found a loss of methylation on the maternal chromosome at imprinting center 2 (IC2) on chromosome 11. During her newborn period, she did not have hypoglycemia. She presented to her primary care physician with a 2.4-kilogram weight loss, new-onset headaches, polyuria, and polydipsia for three months. She also had a viral upper respiratory tract infection a month prior to presentation. Her twin sister did not have similar complaints. Her physical exam including vital signs was reassuring. With the concern for diabetes, further work-up was done which showed an elevated serum glucose level of 681 mg/dL, and hemoglobin A1C of 12.4%. She was admitted for new-onset diabetes. Further labs on admission also showed elevated transglutaminase IgG and positive glutamic acid decarboxylase 65 (GAD65) antibody (level: 444 nmol/L, normal: ≤0.02 nmol/L). Notably, no acidosis was detected in the initial investigations and, unfortunately, due to laboratory error the diabetes antibody panel was cancelled. She was started on a basal-bolus insulin regimen with the diagnosis of new-onset T1DM without ketoacidosis. BWS does not have T1DM as a known characteristic. Hypoglycemia secondary to hyperinsulinemia rather than the opposite, such as our case, is associated with BWS. Due to this, our case is rare, and we found a case report from Europe describing a similar phenomenon. Our patient had a GAD65 antibody being positive which explains having T1DM although there are no studies showing the association of BWS with a positive GAD65 antibody. Our patient also had a viral infection prior to the diagnosis of T1DM which may have triggered autoimmunity. Further, IC2 loss of methylation present in our patient regulates the expression of CDKN1C which has been previously reported to be associated with diabetes. Conclusion Further studies will be required to identify the possible case of T1DM in a patient with BWS. We plan on obtaining a diabetes antibody panel to further assess the genetics of our patient.