PSUN247 Unique Presentation of MODY Type 5

Abstract

Abstract A 46-year-old female with a past medical history significant for a blind vaginal birth defect that required vaginal reconstructive surgery with a partial hysterectomy at 15 years old and Type 2 Diabetes diagnosed at 44 years old. The patient was started on Sitagliptin, metformin 500 mg BID, and glimepiride 2 mg, but she remained poorly controlled with A1C 12.5%. Liver enzymes were elevated with the following values on the liver panel: AST 63 U/L Alt113 U/L bilirubin total 1.0 U/L direct bilirubin 0.3 U/L Alkaline phosphatase 642 U/L. Abdominal ultrasound and serology for chronic liver disease were unremarkable; enhanced MRI of the abdomen showed no abnormalities in the liver and pancreas. CT-guided liver biopsy was performed and pathology revealed diabetic hepatosclerosis. Ultimately, the patient was referred for endocrinology evaluation for poorly controlled diabetes mellites. Blood work was negative for GAD antibodies 65 and anti-pancreatic islet cell antibodies. C peptide level was within normal limits. The patient was not compliant with medications; her A1C continues to range between 11.5 and 8.5 so she was started on subcutaneous insulin. A few years later, the patient presented to the ED for generalized weakness, anorexia, and unintentional weight loss of approximately 40 pounds with a BMI of 17 kg/m2. Bloodwork revealed glucose was 222 mg/dl, and glycated hemoglobin (A1C) was 15.4%, with no acute metabolic disorder (no ketosis). Biochemical analysis reported triglycerides of 174 mg/dL, total cholesterol of 280 mg/dL, HDL of 82 mg/dL, aspartate aminotransferase of 75 U/L, alanine aminotransferase of 117 U/L. alkaline phosphatases 190U/L, Potassium 3.1mEq/L, and magnesium 1.3mEq/L Her electrolytes failed to correct despite adequate replacement; hence nephrology evaluation was warranted. As a result, 24h urine collection was obtained and revealed a Gitelman pattern with salt wasting, K+ wasting, Mg2+ wasting, and no calcinuria. This raised suspicion for MODY type 5. An enhanced MRI of the abdomen revealed her pancreas was missing the distal body and tail as well as bilateral cystic kidney disease. Genetic testing was pursued and demonstrated mutations in the hepatic nuclear factor 1B (HNF1B) gene which confirmed the MODY type 5 diagnosis. The patient was discharged on 11 units of insulin degludec at bedtime in addition to insulin aspart 2 units TID; her A1c improved to 8.3% on her most recent follow-up. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.