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Purpose: To compare the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses. Methods: The clinical characteristics corresponding to pediatric urolithiasis patients that had undergone exome sequencing at our hospital between January 2016 and May 2021 were collected. Genetic analysis results were used to separate patients into positive and negative molecular diagnosis groups. Multivariate logistic regression analyses adjusted for visiting age, sex, ethnicity, province, and body mass index were used to compare differences in medical history, diagnostic imaging findings, and renal function between individuals with and without molecular diagnoses. Results: In total, 194 patients with pediatric urolithiasis of unknown etiology underwent exome sequencing and were included in the present study, of whom 63 obtained urolithiasis-related molecular diagnoses. Relative to cases without a molecular diagnosis, those with a positive molecular diagnosis were more likely to be associated with a positive family history (OR 2.84, 95% CI 1.29–6.29, p = 0.008), consanguineous parents (OR 24.7, 95% CI 1.34–454, p = 0.002), early onset (OR 1.26, 95% CI 1.09–1.45, p < 0.001), nephrocalcinosis (OR 10.6, 95% CI 3.06–36.6, p < 0.001), cast stone (OR 18.9, 95% CI 4.40–81.1, p < 0.001), multiple stones (OR 13.9, 95% CI 6.39–30.2, p < 0.001), bilateral stones (OR 7.04, 95% CI 3.47–14.2, p < 0.001), a lower estimated glomerular filtration rate (OR 1.17, 95% CI 1.07–1.28, p < 0.001), and chronic kidney disease (OR 26.9, 95% CI 1.42–526, p < 0.001). Conclusion: A positive family history, consanguineous parents, early onset, nephrocalcinosis, severe stone burden, and impaired renal function are signals of concern that are suggestive of inherited urolithiasis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of inherited causes in an early onset urolithiasis cohort and each metabolic subgroup. Methods: A retrospective analysis of both metabolic and genomic data was performed for the first 105 pediatric urolithiasis patients who underwent exome sequencing at our hospital from February 2016 to October 2018. Measurements included the diagnostic yield of exome sequencing in the entire cohort and each metabolic subgroup (hyperoxaluria, hypocitraturia, hypercalciuria, hyperuricosuria and cystine stone subgroups). The conformity between molecular diagnoses and metabolic evaluation was also evaluated. Results: The present study involved a cohort of 105 pediatric patients with urolithiasis, from which diagnostic variants were identified in 38 patients (36%), including 27 primary hyperoxaluria and 11 cystinuria. In the metabolic subgroup analyses, 41% hyperoxaluria cases were primary hyperoxaluria caused by monogenic defects, and 100% of the causes of cystine stones could be explained by monogenic defects. However, no appropriate inherited causes were identified for hypocitraturia, hypercalciuria, or hyperuricosuria in the cohort. A high conformity (100%) was obtained between the molecular diagnoses and metabolic evaluation. Conclusion: Exome sequencing in a cohort of 105 pediatric patients with urolithiasis yielded a genetic diagnosis in 36% of cases and the molecular diagnostic yield varies substantially across different metabolic abnormalities. [ABSTRACT FROM AUTHOR]