Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited

Kołbuc, Marcin; Bieniaś, Beata; Habbig, Sandra; Kołek, Mateusz Franciszek; Szczepańska, Maria; Kiliś‐Pstrusińska, Katarzyna; Wasilewska, Anna; Adamczyk, Piotr; Motyka, Rafał; Tkaczyk, Marcin; Sikora, Przemysław; Beck, Bodo B.; Zaniew, Marcin

doi:10.3390/jcm10153265

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…It is also no surprise that hyperuricemia was found to be irrelevant for prediction. In a previous study, we demonstrated its limited value due to a strong association of sUA with kidney function and PTH [17].…”

Section: Discussionmentioning

confidence: 96%

Development of a tool for predicting HNF1B mutations in children with congenital anomalies of the kidneys and urinary tract – a retrospective multicenter study

Kolbuc,

Kolek,

Motyka

et al. 2023

Preprint

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Background The diagnosis of HNF1B disease is a challenge. We aimed to developa 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 into the model, and receiver operating characteristiccurve statistics were used to verify its predictive effect. Results 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 HNF1Bcohort. The above‑mentioned, 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. ConclusionThis study developed a simple tool for predicting HNF1B mutations in children with CAKUT.

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Section: Discussionmentioning

confidence: 96%

Development of a tool for predicting HNF1B mutations in children with congenital anomalies of the kidneys and urinary tract – a retrospective multicenter study

Kolbuc,

Kolek,

Motyka

et al. 2023

Preprint

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“…And hypomagnesemia is often underestimated in children patients [ 17 ]. The presence of hypomagnesemia is associated with renal tubular dysfunction, and hypokalemia, hyperuricemia, and proteinuria are also frequently obtained [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Unusual manifestations of young woman with MODY5 based on 17q12 recurrent deletion syndrome

Cheng¹,

Zhong²,

Li³

et al. 2022

BMC Endocr Disord

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Background Maturity-onset diabetes of the young type 5 (MODY5) is a rare subtype of MODYs. It is caused by mutations of the hepatocyte nuclear factor 1 homeobox b gene (HNF1B). 17q12 recurrent deletion syndrome usually results in MODY5 because of the deletion of HNF1B. These patients often have other clinical manifestations besides diabetes. Refractory hypomagnesemia was a clue for further examination in this patient. But she lacked structural abnormalities of the genitourinary system and neurodevelopmental disorders that are common manifestations in patients with 17q12 recurrent deletion syndrome. Some atypical patients deserved attention. Case presentation A 21-year-old young woman was admitted to our hospital for severe malnutrition and gastrointestinal symptoms. At age 20, she was diagnosed with type 2 diabetes mellitus (T2DM) and was administered oral antidiabetic drugs. Soon afterward, the patient discontinued the medication on her own accord and then went to the hospital again due to diabetic ketoacidosis. After insulin treatment, diabetic ketoacidosis was cured and blood glucose was controlled satisfactorily. But intractable nausea, vomiting, and persistent weight loss were stubborn. Further examination revealed that the patient had hypokalemia and hard rectification hypomagnesemia. Genetic testing revealed about 1.85 Mb heterozygous fragment deletion on chromosome 17 and deletion of exons 1–9 of HNF1B heterozygosity missing was approved. Finally, the patient was diagnosed MODY5. Discussion and Conclusions The 17q12 recurrent deletion syndrome is characterized by MODY5, structural or functional abnormalities of the kidney and urinary tract, and neurodevelopmental or neuropsychiatric disorders. This patient did not have any structural abnormalities of the genitourinary system and neuropsychiatric disorders, which is rare. She had experienced a period of misdiagnosis before being diagnosed with 17q12 recurrent deletion syndrome, and hypomagnesemia was an important clue for her diagnosis. Therefore, diabetic physicians should be alert to a special type of diabetes if patients have unexplained signs and symptoms. The absence of well-known features of HNF1B disease does not exclude MODY5.

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“…In our study, 65.00% of MODY5 patients met the diagnosis of hyperuricemia. Previous studies indicated that hyperuricemia was a common early manifestation of MODY5 in children, but its utility as a predictor of the disease was limited ( 26 ). However, hyperuricemia might serve as a supplement to raise our suspicions about MODY5.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Characteristics and Gene Mutations of Maturity-Onset Diabetes of the Young Type 5 in Sixty-One Patients

Yang

Cui

et al. 2022

Front. Endocrinol.

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AimsMaturity-onset diabetes of the young type 5 (MODY5), a rare disease, is very easy to be misdiagnosed as type 2 diabetes. To get better understanding of the disease, we analyzed the clinical characteristics and gene mutations of MODY5.MethodsPubMed, Cochrane, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: “MODY5” OR “HNF1B maturity-onset diabetes of the young” OR “maturity-onset diabetes of the young type 5” OR “renal cysts and diabetes syndrome”. Clinical characteristics and gene mutations of MODY5 were analyzed. The demography, clinical characteristics, and blood indicators of patients were described utilizing simple summary statistics. Variables were analyzed by t-test, Wilcoxon signed rank test, and Fisher exact test. Spearman’s correlation analysis was used for bi-variate analysis. All tests were two-sided, and a p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows (SPSS).ResultsA total of 48 literatures were included in this study, including 61 eligible patients and 4 different mutations. Of the 39 patients with available body weight index, 15 (38.46%) were underweight, 21 (53.85%) were normal weight and 3 (7.69%) were overweight or obese. Of the 38 patients with available family history, 25 (65.79%) reported a family history of diabetes. Of the 34 patients with available age of diabetes diagnosis, the median age of diabetes diagnosis was 16.00 years old and 88.24% (30/34) of patients were under 25 years old when they were first diagnosed with diabetes. Renal cysts were presented in 72.41%, hypomagnesemia in 91.67%, and pancreatic dysplasia in 71.88% of the patients. Patients with hepatocyte nuclear factor 1B (HNF1B) deletion had lower serum magnesium, serum creatinine, and higher eGFR than patients with other gene mutations, and the difference was statistically significant.ConclusionsThe young onset of diabetes with low or normal BMI, renal cysts, hypomagnesemia, and pancreatic dysplasia should be recommended to genetic testing in order to differentiate MODY5 from other types of diabetes earlier.

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Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited

Cited by 8 publications

References 34 publications

Development of a tool for predicting HNF1B mutations in children with congenital anomalies of the kidneys and urinary tract – a retrospective multicenter study

Development of a tool for predicting HNF1B mutations in children with congenital anomalies of the kidneys and urinary tract – a retrospective multicenter study

Unusual manifestations of young woman with MODY5 based on 17q12 recurrent deletion syndrome

The Clinical Characteristics and Gene Mutations of Maturity-Onset Diabetes of the Young Type 5 in Sixty-One Patients

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