ESPE Abstracts

Introduction: ‘Maturity-Onset Diabetes of the Young ‘(MODY) 9 is a rare subtype of MODY, resulting from mutations in the ‘Paired Box Gene 4’ (PAX4) on chromosome 7q32.1. PAX4 is mainly expressed in pancreatic islet cells, playing a crucial role in the development, differentiation, proliferation, and survival of insulin-producing β-cells during embryonic stages, as well as in β-cell regeneration in adulthood. Mutations in PAX4 can lead to hyperglycemia by increasing glucagon secretion, contributing to a wide spectrum of clinical presentations. While mild cases may only show impaired glucose tolerance, severe cases can progress to renal or retinal complications, and even end-stage renal failure. Patients may exhibit symptoms such as polyuria, polydipsia, weight loss, hyperglycemia, impaired glucose tolerance, and ketoacidosis. Here, we present a case of MODY-9 with a mild clinical course due to a heterozygous mutation in the PAX-4 gene.

Case: A 10-year-old girl presented with polyuria and polydipsia for the past three months, without weight loss. Born at term weighing 3000 grams, with non-consanguineous parents, her family history revealed her uncle's diabetes diagnosis at age 22, initially treated with oral antidiabetic medication before transitioning to insulin therapy; her paternal grandfather used insulin, and her grandmother received oral antidiabetic medication. Physical examination showed height of 138.8 cm [-0.85 standard deviations (SD)], weight of 36.40 kg (-0.19 SD), and BMI of 18.9 kg/m² (0.59 SD), consistent with Tanner Stage III puberty. Laboratory tests indicated fasting glucose of 109 mg/dL, HbA1c of 5.8%, C-peptide of 4.08 ng/mL, and negative diabetes autoantibodies. Fasting glucose and HbA1c levels of her parents were 109/114 mg/dL and 5.3%/5.5%, respectively. Oral Glucose Tolerance Test results were normal. Given the borderline fasting glucose/HbA1c value and family history, the patient received dietary advice and home blood sugar monitoring, showing values between 110-120 mg/dL. Genomic analysis detected a heterozygous change [c.794C>G (p.Pro265Arg)] in exon 8 of the PAX4 (NM_006193.2) gene and the same mutation was also detected in the father. The patient was placed on a diabetic diet, with subsequent normoglycemia and HbA1c levels of 5.5-6%. At the last visit, aged 17 years and 2 months, fasting glucose was 90 mg/dL, HbA1c was 5.7%, and C-peptide was 2.21 ng/mL.

Conclusion: MODY-9 presents a broad clinical spectrum, as exemplified by this case with approximately six years of follow-up, highlighting the role of family history in diagnosis and providing insight into the clinical manifestations of MODY-9.