Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.
Medical Genomic Research Department, King Abdullah International Medical Research Center(KAIMRC), King Saud Bin Abdulaziz University for Health Sciences(KSAU-HS), Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.
Pediatr Nephrol. 2023 Jun;38(6):1801-1810. doi: 10.1007/s00467-022-05784-y. Epub 2022 Nov 21.
Primary hyperoxalurias (PHs) constitute rare disorders resulting in abnormal glyoxalate metabolism. PH-associated phenotypes range from progressive nephrocalcinosis and/or recurrent urolithiasis to early kidney failure.
A retrospective study was conducted for patients with confirmed PH diagnoses from three tertiary centers in Saudi Arabia. Detailed clinical molecular diagnosis was performed for 25 affected individuals. Whole exome sequencing (WES)-based molecular diagnosis was performed for all affected individuals.
The male:female ratio was 52% male (n = 13) and 48% female (n = 12), and consanguinity was present in 88%. Nephrolithiasis and/or nephrocalcinosis were present in all patients. Kidney stones were present in 72%, nephrocalcinosis in 60%, hematuria in 32%, proteinuria in 16%, abdominal pain in 36%, developmental delay in 8%, and chronic kidney disease stage 5 (CKD stage 5) was observed in 28% of the patients. The most common PH disorder was type I caused by variants in the AGXT gene, accounting for 56%. The GRHPR gene variants were identified in 4 patients, 16% of the total cases. Seven patients did not reveal any associated variants. Missense variants were the most commonly observed variants (48%), followed by frame-shift duplication variants (28%).
Characterization of the genetic and clinical aspects of PH in this unique population provides direction for improved patient management and further research. A higher resolution version of the Graphical abstract is available as Supplementary information.
原发性高草酸尿症（PHs）是一种罕见的疾病，导致异常的乙醛酸代谢。PH 相关表型范围从进行性肾钙质沉着症和/或复发性尿路结石到早期肾衰竭。
对来自沙特阿拉伯三家三级中心的确诊 PH 患者进行了回顾性研究。对 25 名受影响个体进行了详细的临床分子诊断。对所有受影响的个体进行了基于全外显子组测序（WES）的分子诊断。
男女比例为 52%男性（n=13）和 48%女性（n=12），88%存在近亲结婚。所有患者均存在肾结石和/或肾钙质沉着症。肾结石见于 72%，肾钙质沉着症见于 60%，血尿见于 32%，蛋白尿见于 16%，腹痛见于 36%，发育迟缓见于 8%，慢性肾脏病 5 期（CKD 5 期）见于 28%。最常见的 PH 疾病是由 AGXT 基因突变引起的 1 型，占 56%。4 名患者（占总数的 16%）鉴定出 GRHPR 基因突变。7 名患者未发现任何相关变异。错义变异是最常见的变异（48%），其次是移码重复变异（28%）。
在这个独特的人群中，对 PH 的遗传和临床方面进行特征描述，为改善患者管理和进一步研究提供了方向。更清晰的图表摘要版本可作为补充信息获取。
