Genotype and Phenotype Analysis in Pediatric Patients with Cystinuria

Abstract

Cystinuria is an inherited disorder characterized by defective renal reabsorption of cystine and dibasic amino acids leading to nephrolithiasis. This study was conducted to analyze the genotypes and phenotypes of pediatric patients with cystinuria. Eight children from Seoul National University Hospital and Asan Medical Center presenting with cystinuria from January 2003 to June 2016 were retrospectively analyzed. Mutational studies were performed by direct sequencing. Two of the 8 were male and 6 were female. The median ages at onset and diagnosis were 1.5 (range, 0.3–13.6) and 2.6 (range, 0.7–16.7) years, respectively. The median followed up was 7.7 (range, 3.4–14.0) years. Mutational analyses were performed in 7 patients and revealed biallelic SLC3A1 mutations (AA genotype) in 4 patients, a single heterozygous SLC3A1 mutation (A- genotype) in 1 patient, biallelic SLC7A9 mutations (BB genotype) in 1 patient, and a single heterozygous SLC7A9 mutation (B- genotype) in 1 patient. Two of the mutations were novel. No genotype-phenotype correlations were observed, except for earlier onset age in patients with non-AA genotypes than in patients with the AA genotype. All patients suffered from recurrent attacks of symptomatic nephrolithiasis, which lead to urologic interventions. At the last follow-up, 3 patients had a mild-to-moderate degree of renal dysfunction. This is the first study of genotypic and phenotypic analyses of patients with cystinuria in Korea.

Clinical profile of a Polish cohort of children and young adults with cystinuria

“…found no significant differences in multiple clinical parameters, such as age at disease presentation or number of urolithiasis episodes when comparing groups of patients with different genotypes [ 10 ]. Similar data were reported for Korea, Czechia, Slovakia, and Greece [ 9 , 14 ].…”

“…Despite this, coverage of most parts of Poland was maintained and thus the cohort is representative of the whole country, ensuring that the results obtained were not biased. In addition, the number of observations from the clinical national data is comparable to those reported in previous studies from Korea, Portugal, France [ 8 ], and Great Britain [ 9–12 ]. All clinical pediatric research centers dealing with tubulopathies in Poland were engaged in the study, making the clinical analysis of pediatric cystinuria patients the first and largest of its kind in Poland.…”

The Urological Association of Asia clinical guideline for urinary stone disease

“…42 Inherited metabolic disorders are often associated with pediatric urolithiasis cases. 43 Adenine phosphoribosyltransferase deficiency, 44 cystinuria, [45][46][47] xanthinuria, 48 Dent disease, 49,50 familial hypomagnesemia with hypercalciuria and nephrocalcinosis, 51,52 and primary hyperoxaluria [53][54][55] cause urinary hypersaturation of insoluble mineral salts, which can inevitably increase the risk of kidney stone formation (LE:4).…”

Diagnostic Approach in Cystinuria: A Case Report

“…In many studies, it has been reported that there is no genotype-phenotype correlation in patients with cystinuria, and also no mutation is shown in 5% of patients. 12,13 Therefore, detection of increased urinary cystine excretion still remains the main tool in assessing the prognosis and deciding on appropriate treatment.…”