Maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY): a 2-year follow-up study of six patients from a single diabetes center.

Objectives: Summarize the clinical phenotypes and genotypic characteristics of Chinese pediatric patients with maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY).

Methods: Retrospective analysis of clinical characteristics, blood biochemical indexes, and genetic testing data was conducted on six children diagnosed with HNF1β-MODY followed in a single institution in Wenzhou from July 2020 to July 2024.

Results: Among the six children, three males and three females with a median age of diabetes onset at 12.3, four presented with pancreatic dysplasia. Extra-pancreatic manifestations included renal structural abnormalities(6/6), hypomagnesemia(6/6), hyperuricemia(4/6), elevated liver enzymes(4/6), hyperlipidemia(3/6), and genital tract malformation(1/6). Genetic testing identified a heterozygous HNF1β exon: 1-9 deletion in one patient, while the other five 17q12 microdeletions. Four children started insulin therapy at diagnosis, demonstrating no progressive decline in insulin secretion function and well-maintained insulin dependency. Six children received oral magnesium supplementation, and blood magnesium levels persisted at the lower limit of normal, without neuromuscular complications. Combined therapy with urinary alkalinizing agents and uricosuric drugs in three patients effectively maintained the serum urate levels, without observed progression. Hepatoprotective therapy decreased liver enzymes in two cases.

Conclusions: The clinical phenotype of HNF1β-MODY encompasses early-onset diabetes mellitus, pancreatic dysplasia, kidney disease, liver dysfunction, and genitourinary tract malformations, with refractory hypomagnesemia and hyperuricemia representing pathognomonic features. Early genetic confirmation can facilitate timely insulin initiation, guide targeted correction of electrolyte imbalances and metabolic disorders, and trigger proactive multi-organ monitoring for disease evolution.