Integration of exome sequencing and metabolic evaluation for the diagnosis of children with urolithiasis.

To investigate the prevalence of inherited causes in an early onset urolithiasis cohort and each metabolic subgroup.

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.

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.

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.

World journal of urology. 2020 Sep 16 [Epub ahead of print]

Yining Zhao, Xiaoliang Fang, Yanjie Fan, Yu Sun, Lei He, Maosheng Xu, Guofeng Xu, Yufeng Li, Yunteng Huang, Yongguo Yu, Hongquan Geng

Department of Pediatric Urology, Children's Urolithiasis Treatment Center of National Health Commission of China, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China., Department of Pediatric Endocrinology/Genetics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China., Department of Pediatric Nephrology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China., Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China., Department of Pediatric Urology, Children's Urolithiasis Treatment Center of National Health Commission of China, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. .