Clinical presentation, biochemical profile, and imaging characteristics of patients with genetically confirmed maturity-onset diabetes of the young (MODY) type 5: Our experience and systematic review

To characterize the clinical features and identify genotype-phenotype correlation in patients with maturity-onset diabetes of the young type 5 (MODY5).

We conducted a retrospective observational study on seven patients with genetically confirmed HNF1B molecular defects from a single center in India. We also performed a systematic review of the literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). Genetically proven MODY5 patients were searched in the English literature published between 1997 and November 2023.

Out of 435 patients with MODY5, 71.7% were diagnosed before the age of 25. A family history of diabetes was present in 73.2%, with three successive generation involvement in 36.1%. Insulin therapy was needed in 81.5%. Diabetic ketoacidosis occurred in 16.6%. Pancreatic structural abnormalities were seen in 54%, often absent tails/bodies. 47.5% showed pancreatic exocrine insufficiency, 56.3% had hyperechoic kidneys, 23.7% had ureteric abnormalities, 12% had nephrocalcinosis/nephrolithiasis, 46.7% of women had uterine abnormalities, and 37.5% of men had epididymal cysts. Hypomagnesemia and hypokalemia occurred in 56.2% and 28.6%, respectively. Patients with 17q12 deletions required more insulin, had more neuro-psychiatric issues, and had a higher prevalence of hypomagnesemia. In contrast, retinopathy was commoner in the mutation group. Renal and genital anomalies and mean eGFR were similar between deletion and HNF1B mutation groups.

Diagnosis of MODY5 is often challenging due to its varied presentation. This study provides a comprehensive analysis of the phenotypic characteristics of such individuals. The findings underscore the importance of considering MODY5 in young patients with diabetes mellitus, especially those with a family history, pancreatic structural abnormalities, and relevant extra-pancreatic features.