Genetic causes of nephrolithiasis and nephrocalcinosis in a pediatric population in Saudi Arabia.
PMID 41203986 | PMCID PMC12852217 | DOI 10.1007/s00467-025-07018-3 · Pediatric nephrology (Berlin, Germany) · 2026 · View on PubMed ↗
BACKGROUND: Nephrolithiasis (NL) and nephrocalcinosis (NC) are common, recurrent conditions globally. While monogenic causes are increasingly recognized, data on their prevalence and spectrum remain limited in Saudi pediatric populations. METHODS: This retrospective cross-sectional study was conducted in our tertiary care center from January 2008 to April 2023. Pediatric patients (0-18 years) with radiologically confirmed NL/NC who underwent genetic testing were included. Clinical, biochemical, radiological, and genetic data were analyzed. Genetic variants were classified using ACMG criteria, and segregation analysis was performed when available. RESULTS: Of 186 pediatric patients diagnosed with NL/NC, 54 (29.03%) underwent genetic testing. Median age at diagnosis was 3 months [IQR: 3-60], with median follow-up 56 months [IQR: 24-108]. Genetic mutations related to NL/NC were identified in 35/54 patients (64.81%), most commonly in CLDN16 (28.57%), SLC2A2 (17.14%), AGXT (11.43%), and SLC12A1 (8.57%). Thirteen novel variants were identified, with eleven linked to NL/NC phenotypes. Eight patients (14.81%) developed kidney failure requiring kidney replacement therapy; CLDN16 was significantly associated with kidney failure and transplant (P = 0.003), and AGXT with liver transplant (P < 0.001). Notably, the MOCS1 gene was found in a patient with early-onset neurological symptoms, hypouricemia, and later confirmed NL/NC. CONCLUSION: Monogenic causes were identified in 35 of 54 (64.81%) Saudi pediatric patients with NL/NC who underwent genetic testing, a prevalence higher than reported internationally, likely due to the high consanguinity rate. Our findings underscore the importance of genetic testing in early-onset NL/NC. We recommend adding MOCS1 to the list of genes associated with monogenic NL/NC.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | CLDN16 | “Genetic mutations related to NL/NC were identified in 35/54 patients (64.81%), most commonly in CLDN16 (28.57%), SLC2A2 (17.14%), AGXT (11.43%), and SLC12A1 (8.57%).” | 0.98 | hgnc_dict_v1 |
| gene | SLC2A2 | “Genetic mutations related to NL/NC were identified in 35/54 patients (64.81%), most commonly in CLDN16 (28.57%), SLC2A2 (17.14%), AGXT (11.43%), and SLC12A1 (8.57%).” | 0.98 | hgnc_dict_v1 |
| gene | AGXT | “Genetic mutations related to NL/NC were identified in 35/54 patients (64.81%), most commonly in CLDN16 (28.57%), SLC2A2 (17.14%), AGXT (11.43%), and SLC12A1 (8.57%).” | 0.98 | hgnc_dict_v1 |
| gene | SLC12A1 | “Genetic mutations related to NL/NC were identified in 35/54 patients (64.81%), most commonly in CLDN16 (28.57%), SLC2A2 (17.14%), AGXT (11.43%), and SLC12A1 (8.57%).” | 0.98 | hgnc_dict_v1 |
| gene | MOCS1 | “Notably, the MOCS1 gene was found in a patient with early-onset neurological symptoms, hypouricemia, and later confirmed NL/NC.” | 0.98 | hgnc_dict_v1 |
| phenotype | renal failure | “Eight patients (14.81%) developed kidney failure requiring kidney replacement therapy; CLDN16 was significantly associated with kidney failure and transplant (P = 0.003), and AGXT with liver transplant (P < 0.001).” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Genetic causes of nephrolithiasis and nephrocalcinosis in a pediatric population in Saudi Arabia. While monogenic causes are increasingly recognized, data on their prevalence and spectrum remain limited in Saudi pediatric populations. RESULTS: Of 186 pediatric patients diagnosed with NL/NC, 54 (29.03%) underwent genetic testing. CONCLUSION: Monogenic causes were identified in 35 of 54 (64.81%) Saudi pediatric patients with NL/NC who underwent genetic testing, a prevalence higher than reported internationally, likely due to the high consanguinity rate.” | 0.95 | saudi_context_rules_v1 |