AUTHOR=Alghamdi Malak , Alhasan Khalid A. , Taha Elawad Areej , Salim Suha , Abdelhakim Marwa , Nashabat Marwan , Raina Rupesh , Kari Jameela , Alfadhel Majid 

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

JOURNAL=Frontiers in Pediatrics

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.569389

DOI=10.3389/fped.2020.569389

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> 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 <italic>SLC3A1</italic> and/or <italic>SLC7A9</italic> 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.</p><p><bold>Patients and Methods:</bold> 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.</p><p><bold>Results:</bold> 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 <italic>SLC3A1</italic> gene. Seven were homozygous and one was compound heterozygous for the <italic>SLC7A9</italic> gene. We have detected 12 genetic variants including five novel variants. <italic>SLC3A</italic>1 gene variant c.1400 T &gt; 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 (<italic>P</italic> = 0.73).</p><p><bold>Conclusion:</bold> 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 <italic>SLC</italic> 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.</p>