Diversity of Phenotype and Genetic Etiology of 23 Cystinuria Saudi Patients: A Retrospective Study

Frontiers in Pediatrics

article

Malak Alghamdi¹  Khalid A. Alhasan²  Areej Taha Elawad¹  Suha Salim²  Marwa Abdelhakim³  Marwan Nashabat⁴  Rupesh Raina⁵  Jameela Kari⁶  Majid Alfadhel⁴ 

[1] Medical Genetics Division, Department of Pediatrics, College of Medicine, King Saud University;Nephrology Division, Department of Pediatrics, College of Medicine, King Saud University;Electrical & Mathematical Science and Engineering Division (CEMSE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST);King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs;Department of Nephrology, Cleveland Clinic Akron General, United States;Pediatric Nephrology Center of Excellence and Department of Pediatrics, College of Medicine, King Abdulaziz University;Division of Genetics, Department of Pediatrics, King Abdullah Specialized Children Hospital, Ministry of National Guard-Health Affairs

关键词: cystinuria;    SLC3A1;    inborn errors of metabolism;    SLC7A9;    nephrolithiasis;    dibasic amino acids;   

DOI  :  10.3389/fped.2020.569389

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Cystinuria is an inborn error of metabolism that manifests with renal stones due to defective renal epithelial cell transport of cystine which resulted from pathogenic variants in the SLC3A1 and/or SLC7A9 genes. Among nephrolithiasis diseases, cystinuria is potentially treatable, and further stone formation may be preventable. We report 23 patients who were identified biochemically and genetically to have cystinuria showing the diversity of the phenotype of cystinuria and expanding the genotype by identifying a broad spectrum of mutations. Patients and Methods: This is a multicenter retrospective chart review, where clinical and biochemical data, genetic analysis and the progress of the disease were documented over five years at two centers from 2014 to 2019. Results: Of 23 patients who were identified biochemically and/or genetically to have cystinuria, 14 (62%) were male. Thirteen patients were homozygous, and two were heterozygous for the SLC3A1 gene. Seven were homozygous and one was compound heterozygous for the SLC7A9 gene. We have detected 12 genetic variants including five novel variants. SLC3A 1 gene variant c.1400 T > A (p.Met467Lys) is found in 38% of our cohort. Although 21 patients required surgical intervention, none developed ESRD. The number of stone episodes per year varied widely (median frequency of 0.45 stones/ per year, range between 0.06 and 78.2), with no significant difference in stone events per year between sexes ( P = 0.73). Conclusion: Despite the high rate of consanguinity in Saudi Arabia, there was a broad spectrum of genetic variants. Most of our patients are homozygous recessive for SLC genes with multiple generations affected which indicates early screening and prevention of disease in these families. Phenotypic heterogeneity is well documented in our cohort even with the same genotype and the first stone episode age was variable but most commonly seen in the first decade of life.

【 授权许可】

CC BY