Maturity Onset Diabetes of the Young Masquerading as New Onset Diabetes Mellitus Type 1

Abstract

Introduction:/background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders with autosomal dominant mode of inheritance. Mutation in hepatocyte nuclear factor-1β (HNF-1β) gene results in an error of embryonic development of pancreas and nephron, leading to MODY type 5. MODY 5 accounts for 1% of maturity-onset diabetes of the young. It has peak incidence in adolescence/early adulthood, and is associated with renal pathology. Clinical Case: A 15-year boy with history of hypertension and Hashimoto thyroiditis with normal thyroid function was referred for Hb A1C of 6.7% (< 6.4%). Physical exam was remarkable for normal weight at 64%, normal BMI at 83%, absence of thyromegaly or acanthosis nigricans. Diabetes was confirmed by 2 hour Oral Glucose Tolerance Test study (baseline glucose 154 mg/dL (<126 mg/dL), 2 hour glucose 384 mg/dL (<140 mg/dL)). Small doses of insulin (total daily dose 0.1 units/kg/day) resulted in good glucose control. Further labs were significant for weakly positive TTG and GAD antibodies (tTG Ab IgA 55.5 U/mL (<4.0 U/mL), GAD-65 Ab 0.05 nmol/L (< 0.02 nmol/L)), positive TPO (0.0 - 34.9 IU/mL) and detectable ATA antibodies 45.8 IU/mL (0.0 - 40.0 IU/mL), C-peptide 2.9 ng/mL (0.9–7.1 ng/mL). Islet cell, Insulin and Zinc transporter 8 antibodies were negative. Over the next few months he was weaned off insulin and subsequently he had a high insulin of 29.43 uU/mL (3.0 - 17.0 uU/mL) with glucose level of 169 mg/dL. Renal US was performed as part of the work up for hypertension and revealed a small right calculus with no hydronephrosis and a small 8-mm cortical cyst in the right kidney. Urinalysis showed microalbuminuria. Upper GI endoscopy and colonoscopy with biopsy ruled out celiac disease. Presumptive diagnosis of MODY was entertained despite positive TPO, ATA, TTG and GAD antibodies suggesting autoimmune endocrinopathies. His Hb A1C levels were in the range of 5.7 to 6 % during the 15 months of follow up. Genetic testing for MODY resulted in heterozygous deletion of exons 1–9 of the HNF1B gene consistent with MODY5. Conclusion: This is a case of MODY 5 with weakly positive GAD 65 antibodies that was initially misdiagnosed as type 1 diabetes. The presence of weakly positive antibodies should not preclude a work up for MODY in a patient who does not have the clinical features of classic type 1 DM.