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Cystinuria is a genetic disorder that causes recurrent nephrolithiasis. It is the most common type of monogenic stone disease accounting for 6%-8% of pediatric nephrolithiasis. Due to recurrent episodes of nephrolithiasis, it is associated with a very high prevalence of chronic kidney disease. Life-long medical treatment to reduce stone formation i...
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Context 1
... b 0,+ AT amino acid transporter (encoded by SLC7A9 on chromosome 19q13.1). 11 Cystinuria is classified into 3 types (A, B, and AB) based on the genetic abnormality (Table 1). Type A patients have SLC3A1 mutations, type B patients have SLC7A9 mutations, and type AB patients have mutations in both SLC3A1 and SLC7A9. ...Similar publications
Background: CHARGE syndrome (CS) is a single-gene genetic disorder with multiple organ malformations caused by a variant of the chromodomain helicase DNA-binding protein 7 (CHD7) gene on chromosome 8q12.1. In this study, we aimed to investigate new variants that have emerged in these cases compared with typical CS and the relationship between the g...
Citations
... This tubulopathy is characterized by a defect in tubular reabsorption, leading to abundant urinary excretion of COLA-type dibasic amino acids, such as cystine, ornithine, arginine and especially lysine. The prevalence of this pathology is 1/7000 and the average age of first kidney stone is 13 [33]. The reason why urolithiasis begins postnatally in childhood is that the pH of fetal urine is +/-7, preventing cystine stones formation. ...
... In older children, cystinuria is usually defined as >315 mg cystine/g creatinine. In younger children who cannot perform 24-h collections, there are age-related standards for first-morning urine cystine concentration per gram of creatinine Normal cystine concentrations in younger children are as follows [7]: age <1 month: <80 mg cystine/g creatinine; age 1 month -1 year: <52 mg cystine/g creatinine; age >1 year: <35 mg cystine/g creatinine. ...
Cystinuria is an inherited metabolic disorder progressing with recurrent kidney stones due to impaired reabsorption of dibasic amino acids and arises from mutations in the SLC3A1 and SLC7A9 on chromosome 2. Here, we present the case of a 1-year 10-month-old male child with recurrent episodes of urinary tract infections. On evaluation, duplex kidneys and a large bladder calculus were found which was surgically managed. Stone analysis and the genetic study were suggestive of cystinuria.
... Cystinuria, a variably autosomal recessive or dominant genetic condition, is responsible for 1-2% of adult nephrolithiasis and up to 6-8% of paediatric nephrolithiasis worldwide [1]. Mutations in cystinuria-related genes SLC3A1 and SLC7A9 are causative of the disease, which results in a defective reabsorption of cystine and dibasic amino acids ornithine, lysine and arginine in the proximal tubule of the kidney, with crystal deposition in the distal tubule and formation of cystine stones [2••]. ...
... Among these, 36 did not meet the inclusion criteria and were excluded from the review. Reasons for exclusion were case reports (3), in vivo studies (1), reviews (7), genetic studies (5), studies on adverse events (1), studies on treatment modalities trends over time (1), studies in which cystine stones were excluded (4), studies not specifically focused on cystine stones (11) and not specifically on paediatric patients (3). Among studies including different stone compositions, we reported the overall number of patients and the number or proportion of cystine stones. ...
Purpose of Review
We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence.
Recent Findings
A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8–51%, 14–27% and 12.9–15.4% with SWL, URS and PCNL, respectively.
Summary
Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods.
Cystinuria is a rare congenital disorder characterized by the formation of cystine stones in urinary system, mainly kidneys and urinary tract. It follows the autosomal recessive inheritance pattern, where both of the parents contain the mutant allele. Cystine is an oxidized dimeric form of amino acid cysteine, shining crystal of greenish-yellow color sized >5mm. A minor genetic defect in SLC3A1 gene, downregulate the cystine transporter, rBAT protein, to absorb cystine and other dibasic amino acids in proximal tubule of nephron, causing Cystinuria. Computational and molecular analysis of SLC3A1 gene was performed to identify the deleterious missense single nucleotide variations (mSNVs) linked with Cystinuria in Pakistani population. In silico analysis of whole SLC3A1 gene nsSNPs has revealed that the exon 1, 6 and 10 are the hotspot areas, which potentially alter the protein structure and function. Three SNVs including one synonymous SNV A186C in exon 1, and two mSNVs including G314T in exon 1 and G44972A in exons 10 were identified. Both mSNVs were confirmed by ARMS PCR in all the 68 samples. The results have shown that 10% of the patients have G314T, 16% have G44972A and 74% of the patients have both of these mSNVs. Both of these mSNVs were involved in the structural and functional deterioration of rBAT protein. Additionally, computer aided drug designing tools were used to design diaminobenzylpyrimidine drug around the mutant residues which exhibit the lowest binding affinity with the target as compared to the previously reported cystine binding thiol drugs. In future, the present study could be extended to a large scale for mass screening of reported SNVs and mSNVs which, ultimately, lead to the development of knockouts for the functional studies and treatments.
