SAT-688 Rare Case of 48 XXYY Syndrome with Suspected Type 1 Diabetes Mellitus

Abstract

BACKGROUND: 48 XXYY syndrome is a rare aneuploidy characterized by the presence of an extra X and Y chromosome in males. Patients share features of Klinefelter syndrome such as tall stature, hypogonadism, congenital malformations and neurocognitive issues. Hypogonadism may cause abdominal adiposity hence increasing risk of insulin resistance and type 2 diabetes mellitus (DM). Klinefelter syndrome has been associated with certain autoimmune diseases however there is no autoimmune disease link described with XXYY syndrome. We present a patient with XXYY polysomy with insulin requiring DM.Clinical Case: A 26-year-old intellectually disabled male with history of XXYY polysomy presented with seizures and was evaluated for DM management. At age 18, he was noted to have hyperglycemia while undergoing dental extractions for brittle enamel leading to the diagnosis of DM. He was initiated on oral medications for a short period of time and transitioned to insulin due to significant hyperglycemia. Endocrine evaluation at the time also revealed hypergonadotropic hypogonadism and evaluation for Klinefelter syndrome revealed 48 XXYY aneuploidy.Patient’s history was significant for poorly controlled hyperglycemia with HbA1C ranging in 12–14% range in the last few years. History was negative for diabetic ketoacidosis (DKA) as per his primary endocrinologist, despite being noncompliant with his insulin therapy. History was negative for retinopathy, nephropathy or macrovascular complications, although he did have distal extremity paresthesia. On exam, he was noted to be edentulous with tall stature, BMI 21.7, facial dysmorphism, pes planus and 5th-digit clinodactyly bilaterally. Family history was positive for type 2 DM in father and prediabetes in mother.He presented with seizures and was diagnosed with brain abscess. Hyperglycemia was initially managed with IV insulin, followed by basal/bolus therapy. Fasting labs 20 hours after receiving insulin glargine showed glucose of 284 mg/dL, C-peptide 0.6 ng/mL (ref range: 0.8–3.5), proinsulin less than 1.6 pmol/L (less than 8.0), insulin 4 uIU/mL (3–19) suggestive of type 1 DM. Anti-GAD65 and anti-ICA antibody levels were negative. Additional antibody evaluation for type 1 DM (islet antigen 2, insulin autoantibody, micro-insulin and zinc transporter 8) is currently pending at the time of writing.Conclusion: Prevalence of XXYY syndrome is 1:18 000–1:40 000 in males. There are few case reports describing the association of type 2 DM with this syndrome. Our patient’s low BMI, low insulin and C-peptide with hyperglycemia indicate type 1 DM, although the absence of DKA in the setting of noncompliance suggests residual beta cell function or maturity onset diabetes of the young (MODY). Neither T1DM nor MODY has been reported with 48XXYY previously. Clinicians should be aware of this association as it has implications in terms of management of DM.