Background: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). Methods: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. Results: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy. Conclusions: Hyperuricemia is an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.

Objective: Congenital defects/diseases Background: Maturity onset diabetes of the young (MODY) usually presents in patients under the age of 25 years and is an autosomal dominant condition associated with mutations in the hepatocyte nuclear factor 1 alpha gene, glucokinase gene, or hepatocyte nuclear factor 4 alpha gene. This report is of a series of 4 cases from Poland of MODY type 5 associated with mutations in the hepatocyte nuclear factor 1 beta (HNF1B) gene, including a 13-year-old boy and adult men aged 33, 34, and 35 years. Case Reports: Three cases were diagnosed late, in patients in their mid-thirties. In two patients, the initial presentation was symptomatic diabetes complicated by ketoacidosis and hyperglycemic hyperosmolar state. Renal cysts were found in all patients, and pancreatic hypoplasia in 3 patients. All patients except 1 were negative for autoantibodies; 1 presented with hypomagnesemia. Insulin therapy was instituted in all cases. The combination of family history, imaging study results, and biochemical characteristics led to the decision to perform genetic analysis, which was conducted in 2 cases at diagnosis, and in the 2 remaining patients at 1 month and 2 years after diagnosis, respectively. Follow-up data revealed hypomagnesemia and/or hypermagnesuria in all patients. Conclusions: We present 3 young men over 25 years and 1 boy with HNF1B-MODY. Although rare, autosomal dominant gene associations should be considered in young patients with diabetes who present with renal/pancreatic anomalies and low serum magnesium. Unusual presentation and the presence of autoantibodies should not eliminate the possibility of a HNF1B defect.

Background: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT). Methods: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect. Results: A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut − , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation. Conclusions: This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT. Graphical

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.