O-19 A YOUNG WOMAN WITH HYPOPLASTIC PANCREAS: A RARE CASE OF PDX1 GENE-RELATED MODY TYPE 4

Abstract Introduction Maturity-onset diabetes of young (MODY) is an autosomal dominant disorder that causes insulin deficiency without autoimmunity or insulin resistance. Many cases are misdiagnosed as type 1 or type 2 diabetes due to its overlap in clinical presentation. The PDX1 gene encodes a transcription factor called Pancreatic and Duodenal Homeobox 1 (PDX1), which plays a vital role in the formation, differentiation, and function of the pancreas, especially its endocrine beta cells. Although PDX1 gene variants are recognized as a cause of MODY, their prevalence is extremely rare. We present the first reported case of diabetes caused by a PDX1 gene variant (MODY type 4) in Bangladesh. Clinical Case A 21-year-old woman was referred to the 'Diabetes in Young' clinic at Bangladesh Medical University, Dhaka, after a recent diagnosis of diabetes. She presented with typical symptoms of diabetes but showed no evidence of ketosis. The patient reported a long-standing history of passing oily stools but denied any current or prior abdominal pain. Her father had been diagnosed with diabetes at age 50, while her mother was normoglycemic. She had three siblings, none of whom had diabetes. The patient was unable to specify the glycemic status of her maternal or paternal uncles, aunts, or grandparents. The patient was lean (weight 43 kg, BMI 17.3 kg/m², waist circumference 76 cm, waist-to-hip ratio 0.9) and normotensive (blood pressure 90/60 mm Hg). There was no evidence of acanthosis nigricans, and systemic examinations were unremarkable. Laboratory tests revealed low fasting C-peptide, negative results for islet autoantibodies (Anti-GAD65, ZnT8, and IA-2) and low lipase levels (Table 1 and 2). An abdominal X-ray revealed no pancreatic calcification. Imaging studies, including CT and ultrasound, indicated a small pancreas, consistent with pancreatic hypoplasia (only the head of the pancreas was visible, with the tail replaced by fatty tissue; Figure 1). The patient responded well to a low dose of premixed insulin and maintained satisfactory glycemic control (HbA1c 7.7%, plasma glucose: fasting 4.2, postprandial 5.6 mmol/L). She also needed pancreatic enzyme supplementation which improved her steatorrhea. Next-generation sequencing of the MODY-gene panel identified a missense mutation in the PDX1 gene (c.773A>G), which was classified as ‘likely pathogenic’ in the ClinVar database. Conclusion This case highlights the importance of considering genetic causes in young-onset diabetes, particularly when the clinical presentation does not fit conventional patterns of type 1 or type 2 diabetes. The identification of a PDX1 gene mutation (c.773A>G) as the cause of diabetes in this patient underscores the relevance of genetic testing in diagnosing MODY, a condition often overlooked in clinical practice.Figure 1:CT scan showing pancreatic hypoplasia, with only the head of the pancreas visible (H), while the tail is replaced by fatty tissue (T)  Table-1:Laboratory investigations of the patient at diagnosisHbA1c: Hemoglobin A1c; PG: Plasma Glucose; Anti GAD65: Anti-Glutamic Acid Decarboxylase 65; Anti ZnT8: Anti-Zinc Transporter 8; Anti IA2: Anti-Islet Antigen-2; LDL: Low-Density Lipoprotein; HDL: High-Density Lipoprotein  Table 2:Other laboratory investigations of the patient at diagnosisSGPT: Serum Glutamate Pyruvate Transaminase; ESR: Erythrocyte Sedimentation Rate; CRP: C-reactive protein