CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.

No abstract

Case series Patients: Male, 13-year-old • Male, 33-year-old • Male, 34-year-old • Male, 35-year-old Final Diagnosis: HNF1B nephropathy • HNF1B-MODY type 5 Symptoms: Diabetic ketoacidosis • elevated liver enzymes • hyperglycemia • hyperuricemia • hypomagnesemia • positive family history • renal cysts • renal magnesium wasting • weigh loss Medication:— Clinical Procedure: Genetic analysis • islet autoantibodies Specialty: Endocrinology and Metabolic • Nephrology 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 autoanti-bodies; 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: 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.

Background and Aims Hyperuricemia is recognized as an important feature of HNF1B nephropathy, and could serve as a good marker of the disease facilitating selection of patients for genetic testing. However, neither the casual relationship nor its predictive value have been proven yet. We thus decided to assess this in a cohort of children with renal malformations with (mut+) and without HNF1B mutations (mut-). Method We performed a retrospective analysis of clinical and genetic results of pediatric patients tested for HNF1B mutations, whose data were collected in a national registry. Hyperuricemia was assessed by using the newest, age- and gender-dependent reference values for serum uric acid (sUA) in children. Results A total of 108 children were included into the study comprising 43 mut+ patients, and 65 mut- subjects. Mean sUA was higher in mut+ than in mut- subjects (p = 0.006), and hyperuricemia was more prevalent in those with HNF1B mutations (42.5% vs. 15.4%, p = 0.002). Renal phenotype analysis revealed renal hyperechogenicity and multicystic dysplastic kidney disease were more frequent in mut+ patients, but no influence of any renal features/phenotypes on hyperuricemia was found. The two patient cohorts were different with regard to pancreatic anomaly (p < 0.001), glucose metabolism disorders (p = 0.003), hypomagnesemia (p < 0.001), and hyperparathyroidism (p < 0.001). In a multivariate linear stepwise regression model, eGFR, fractional excretion of uric acid, impairments in glucose metabolism and pancreatic anomaly were found to be independent predictive variables of sUA (R2=0.67, F=13.27, p < 0.001). Mutation was not identified as a determinant of sUA. After exclusion of patients with hyperglycemia and/or pancreatic malformations, the difference in hyperuricemia prevalence did not persist between mut+ and mut-. Potential of hyperuricemia for mutation prediction was tested in a model with hypomagnesemia and hyperparathyroidism, which showed an accuracy of 85% (sensitivity: 83%, specificity: 86%). Adding hyperuricemia to the model did not increase the accuracy (79%; sensitivity: 77%, specificity: 82%). Information gain, which informs selective potential of each parameter, was the lowest for hyperuricemia (0.34 compared with 0.99 and 0.63 for hyperparathyroidism and hypomagnesemia, respectively). Conclusion Hyperuricemia is relatively common in children with HNF1B mutation, however its direct association with this molecular defect remains still unproven. Its dependence on renal function and hyperglycemia diminishes the utility as a clinically useful marker for predicting HNF1B disease.