Determination of etiology of pediatric urinary stone disease by multigen panel and evaluation with metabolic screening

Determination of Etiology of Pediatric Urinary Stone Disease by Multigen Panel and Evaluation with Metabolic Screening Introduction: It is known that urinary stone disease is increasing in children, and genetic, metabolic, and environmental factors play a role in its etiology. In this study, we investigated the multi-gen panel and metabolic evaluation together because it is a genetically heterogeneous disease. Methods: Between March 2016 and July 2019, 48 children who were operated and followed for the urinary system stone disease in Çukurova University Faculty of Medicine, Department of Urology, were included in the study. Children with known metabolic disorders were excluded from the study. A detailed anamnesis was taken from each patient, and the positive family history was questioned. Blood and urine samples were taken, and metabolic evaluation was done. 2 cc peripheral blood samples were collected from the patients selected within Çukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center), and DNA isolation was performed. Analysis of the obtained sequence data was performed. Results: Of the 48 children included in the study, 29 (60.4%) were boys and 19 were girls (39.6%). The average age was 60 ± 50 (12-192) months. It was observed that 28 (58.3%) of the patients included in the study had positive family history. The most common metabolic abnormality was hypernaturia (n: 30 (62.5%)). This includes hyperuricosuria (n: 23 (47.9%)), hypercalciuria (n: 19 (39.6%)), hyperoxaluria (n: 18 (37.5%)), hypomagnesuria (n: 13 (27.1%)) cystinuria (n: 10 (20.8%)) and hypocitraturia (n: 5 (10.4%)) were followed. As a result of the new generation sequencing studies carried out with the multi-gene panel, as a result of bioinformatical analysis on the data, quality controls were performed, a total of 21 clinically significant variants were detected in 8 different genes. The weighted distribution of 21 variants detected by genes is five variants (23.8%) in the SLC3A1 gene, four variants (19%) in the SLC6A20 gene, and 3 (14.3%) in the SLC7A9 and SLC26A1 genes. Conclusions: It is essential to identify underlying metabolic and genetic risk factors in children with urinary stone to prevent stone formation again and to apply the most effective treatment methods Key words: Child urology, Nephrolithiasis in children, Genetics in nephrolithiasis, Etiology of stone disease, Urinary system stone disease