Abstract Background Pathogenic variants in the HNF1B gene cause a multi system disorder encompassing organ abnormalities—primarily affecting the kidneys and pancreas—as well as metabolic disturbances, collectively referred to as HNF1B -related disease. While maturity-onset diabetes of the young type 5 is a well-recognized manifestation, neonatal diabetes mellitus (NDM) associated with HNF1B is exceedingly rare, and has only been reported in patients harboring single nucleotide variants. Case presentation We describe two unrelated female children presenting with transient NDM caused by a complete HNF1B gene deletion. Both developed hyperglycemia within the first days of life requiring short-term insulin therapy, followed by spontaneous normalization of glycemia. However, their subsequent phenotypes diverged significantly. The first patient exhibited bilateral renal dysplasia while maintaining normal neurodevelopment. In contrast, the second patient developed later-onset cystic kidney disease, neurodevelopmental delay, and dysmorphic features, consistent with a broader 17q12 deletion syndrome spectrum. Although, in both cases, kidney abnormalities and extra-renal features (NDM, hypomagnesemia, hyperuricemia) were observed, both patients experienced a delay in diagnosis. On follow-up, serial oral glucose tolerance tests (OGTT), HbA1c assessments, and glucagon stimulation tests to date demonstrated preserved β-cell function, with the exception of hyperglycemia in 30–60 min of the extended OGTT in one patient. Conclusions These two cases represent the first report of transient NDM due to HNF1B deletion. Our findings broaden the molecular and clinical spectrum of HNF1B -related diabetes, and emphasize the importance of considering HNF1B defects in children with transient neonatal hyperglycemia.
Kołbuc et al. (Thu,) studied this question.