MON-570 A Diagnosis In Disguise- Hidden Clues Of Young-onset Diabetes

Abstract Disclosure: N. Mangam: None. P. Deb: None. S. Devireddy: None. S. Nalla: None. K. Nutakki: None. T. Nayani: None. Background: Maturity-onset diabetes of the young (MODY) is most prevalent monogenic diabetes,i.e;1-5% of all diabetes cases. Most of the MODY cases are initially labelled as T1DM or T2DM based on response to insulin or oral hypoglycemic agents respectively. Diagnosing MODY is important for Precision Medicine approaches to improve quality of life. Next-generation sequencing has made genetic diagnosis affordable. Here we report an interesting case of genetically proven MODY-5 with HNF1B gene deletion. Clinical Case: A 23 years male who is a known case of diabetes mellitus since 5 years, was admitted with abdominal pain, vomiting and uncontrolled blood glucose since 6 months. He had history of orchidopexy for right undescended testes at 8 years of age and cystoscopic deroofing of seminal vesical cyst at 21 years of age. Father had T2DM at 51 years. On examination vitals were stable, BMI was 13.6 kg/m2 (underweight), no acanthosis, SMR- Tanner stage 4. Systemic examination was normal. Laboratory investigations showed RBS-280mg/dl, HbA1c-9.7%, ABG - no acidosis (pH-7.49), liver function tests- elevated total and direct bilirubin (TB-2mg/dl, DB-1.68mg/dl), elevated transaminases (SGPT-195 IU/L, SGOT- 89 IU/L) and alkaline phosphatase (251 U/L), amylase was 39 U/L, lipase was 6.4 U/L, urine ketones were negative. Autoimmune hepatitis panel and hepatitis B and C were negative. CECT Abdomen showed dorsal pancreatic agenesis and bilateral Bosnaik type 1 renal cortical cysts. Anti-GAD antibodies were negative, C-peptide was 0.8 ng/ml and fecal elastase was low. In view of young onset diabetes, agenesis of dorsal pancreas, right cryptorchidism, renal cortical cysts, cyst in seminal vesical and liver dysfunction- considered MODY-5. Whole exome sequencing revealed HNF1B gene deletion in chromosome 17. On evaluation magnesium was low (1.2 mg/dl) with high (7.5%) fractional excretion of Mg. We have treated with basal-bolus regimen of insulin and magnesium supplementation. Gastroenterologist has advised pancreatic enzyme replacement therapy and abdominal symptoms were considered functional. Psychiatrist has diagnosed depression and advised anti-depressants. He improved symptomatically, gained weight and is having good glycemic control. Conclusion: MODY-5 is caused by heterozygous variants in HNF1B gene, with autosomal dominant inheritance and 40% of HNF1B variants are de novo. In any young-onset (<35 years) diabetes with negative islet auto-antibodies and c-peptide >200pmol/L (0.6ng/ml), MODY should be suspected. Surveillance of extra-pancreatic phenotypes like chromophobe-type renal cell carcinoma (annual abdominal USG), genetic testing and family counseling are essential. In our case pancreatic imaging helped in diagnosis, as mutations in HNF1B result in aplasia of pancreatic body and tail. Therefore pancreatic imaging could help guide molecular and genetic investigation. Presentation: Monday, July 14, 2025