SUN-130 A Not-So-Simple Work-Up of Diabetes: A Case of MODY 5

Abstract

Introduction: Maturity-onset diabetes of the young 5 (MODY-5) is a rare type of inherited diabetes mellitus. It is an autosomal dominant disease, manifesting as a clinically heterogeneous disorder with a lack of autoantibodies. On the molecular level, MODY 5 is due to defects of hepatocyte nuclear factors 1B (HNF1B), which not only cause structural abnormalities, but also intrinsic organ dysfunction in the kidneys, liver, and pancreas as well. Case: This is a 33 year old female presented for diabetes type 2 management. Her past medical history originated at the age of 7, diagnosed with short ureters with reflux leading to frequent pyelonephritis, requiring reconstructive surgery. At 15, found to have high liver enzymes, which have had variable and persistent elevation; she had 4 liver biopsies, which were pathologically unremarkable and no cause found. At 27, diagnosed with type 2 DM based on her HbA1c being >7 and initiated on metformin. Recently was also diagnosed with PCOS after a first trimester missed abortion and subsequent infertility. Abdominal US subsequently revealed bilateral renal cysts. Family history was remarkable for type 1 diabetes in her father, type 2 diabetes in her sister and maternal uncle, and renal dysfunction in her niece. Physical exam was unremarkable, and BMI was 19.53 kg/m2. Laboratory workup revealed elevated liver enzymes (Alkaline Phosphatase: 445 U/l; Bilirubin: 1.7 mg/dl, ASL: 106 U/L, ALT 248 U/L). A1C was 5.3% at that time. Based off the presentation and exam, it was felt that her disease process did not fit the classic paradigm of type 2 diabetes mellitus, no obesity, no hypertension and no dyslipidemia. This prompted autoimmune diabetes screening which was negative. A MODY Sequencing Panel was then performed, which was positive for MODY type 5; she was found to be heterozygous in the HNF1B gene, c.544+1G>A variant. Given her diagnosis, an insulin regimen was initiated but due to allergic reaction, she was then converted to glipizide orally. She is now following with medical genetics. Conclusion: MODY is not commonly seen in the diabetes population, where prevalence accounts for 2 to 5 % of known diabetics. MODY-5 is a more uncommon subset in the population with MODY, manifesting as 5-10% of such cases. As such, many MODY patients are often misclassified has having either type 1 or type 2 diabetes. Given other organ dysfunctions affected by MODY-5, a lack of diagnosis of this condition can delay monitoring and treatment of the disease. As such, recognition of MODY should be increased, as is need for early screening for patients if the disease is suspected. Citation: Dubois-Laforgue, D,. et al. (2017). Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B ( HNF1B ) Molecular Defects. Diabetes Care, 40(11), 1436-1443. doi:10.2337/dc16-2462. PMID: 28420700