7316 A Unique Presentation of Diabetes Mellitus in an 8-Year-Old Male Positive For 3 Different Mutations Related to MODY

Abstract

Abstract Disclosure: R. Senguttuvan: None. A. Pamfil: None. Background: Maturity-Onset Diabetes of the Young (MODY) is the most common form of inherited non-autoimmune diabetes mellitus, characterized by autosomal dominant inheritance, young age at onset and beta cell dysfunction. There are at least 14 MODY mutations and we present a pediatric case not meeting criteria for type 1[T1DM] or type 2 diabetes mellitus[T2DM], who tested positive for mutations in 3 different genes known to cause MODY. Case: An 8-year-old male, born full term, 2776 grams and 48.3 cm, without history of neonatal hypoglycemia or hyperglycemia, was referred for new onset diabetes mellitus management. While undergoing evaluation for abdominal pain and constipation, he was found to have a fasting glucose of 126 mg/dL (7 mmol/L) and hemoglobin A1C of 6.5%. He endorsed polyuria, but no polydipsia. He had no clinical signs of insulin resistance (e.g., acanthosis nigricans) and a BMI of 23.65 kg/m2, at the 97th percentile. Family history is positive for diabetes mellitus requiring insulin, in father (diagnosed at 11 years) and paternal grandmother and T2DM in paternal aunt. Laboratory evaluation was negative for all 5 antibodies (GAD, IA-2, Anti-islet cell antibody, Zinc Transporter 8 and Insulin antibodies) and revealed an insulin level of 15.9 uIU/mL (RR: <2.0-13.0) and C peptide: 2.3 ng/mL (RR: 1.1-4.4). Lacking diagnostic criteria for T1DM or T2DM, genetic testing was performed. Patient tested heterozygous for mutations in 3 genes known to cause MODY: GCK [(c.350 G>T p. (G117V)], ABCC8 [(c.2270 C>G p.(T757R)], and HNF1B [(c.68A>G p.(K23R)], all variant of uncertain significance. Over an 8-month period, patient's weight decreased from 98 lbs. (44.9 kg) to 90 lbs. (41.1 kg) after meeting with our dietician and implementing healthy dietary changes, and his beta cell function markers improved from diagnosis: Fasting insulin (4.5 uIU/mL), C peptide (1.3 ng/mL), and glucose 119 mg/dL; Hemoglobin A1C remained relatively stable at 6.1%. A kidney ultrasound was normal. No medical intervention were started yet, and patient is being monitored clinically and biochemically every 3-4 months. Discussion: Clinical monitoring over time, genetic testing in the parents, are critical in this patient’s long-term treatment plan and prognosis. To our knowledge, this may be the first case of diabetes mellitus in a pediatric patient, positive for mutations in 3 different genes known to cause MODY. South Texas has one of the highest incidences of T2DM in the USA. In addition to screening for genetic forms of diabetes, in patients with negative T1DM antibodies and atypical phenotype for T2DM, we should consider genetic screening in mildly obese pediatric and young adult patients without significant acanthosis nigricans, who were already diagnosed as T2DM. Presentation: 6/1/2024