Marcin Tkaczyk1,2, Katarzyna Gadomska-Prokop3, Iga Załuska-Leśniewska4, Kinga Musiał5, Jan Zawadzki3, Katarzyna Jobs6, Tadeusz Porowski7, Anna Rogowska-Kalisz1, Anna Jander1, Meritrafat Kirolos1, Adam Haliński8, Aleksandra Krzemień9, Agnieszka Sobieszczańska-Droździel10, Katarzyna Zachwieja11, Bodo B Beck12, Przemysław Sikora10, Marcin Zaniew13. 1. Department of Pediatrics, Immunology and Nephrology, Polish Mother's Memorial Hospital Research Institute, Łódź, Poland. 2. Division of Didactics in Pediatrics, Medical University of Łódź, Łódź, Poland. 3. Department of Nephrology, Transplantation and Hypertension, Children's Memorial Health Institute, Warsaw, Poland. 4. Department of Pediatric Nephrology and Hypertension, Medical University of Gdańsk, Gdańsk, Poland. 5. Department of Pediatric Nephrology, Medical University of Wrocław, Wrocław, Poland. 6. Department of Pediatrics, Allergology and Nephrology, Military Medical Institute, Warsaw, Poland. 7. Department of Pediatrics and Nephrology, Medical University of Białystok, Białystok, Poland. 8. Department of Clinical Genetics and Pathology, University of Zielona Góra, Zielona Góra, Poland. 9. Department of Pediatric Nephrology, Upper-Silesian Centre for Child's Health, Katowice, Poland. 10. Department of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland. 11. Department of Pediatric Nephrology, Collegium Medicum Jagiellonian University, Krakow, Poland. 12. Institute of Human Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany. 13. Department of Pediatrics, University of Zielona Góra, Zielona Góra, Poland.
Abstract
BACKGROUND: Cystinuria is an inherited disorder that results in increased excretion of cystine in the urine. It accounts for about 1-2% of pediatric kidney stones. In this study, we sought to identify the clinical characteristics of patients with cystinuria in a national cohort. METHODS: This was a retrospective study involving 30 patients from the Polish Registry of Inherited Tubulopathies. Initial data and that from a 6-month follow-up were analyzed. Mutational analysis was performed by targeted Sanger sequencing and, if applicable, MLPA analysis was used to detect large rearrangements. RESULTS: SLC7A9 mutations were detected in 15 children (50%; 10 males, 5 females), SLC3A1 mutations in 14 children (47%; 5 males, 9 females), and bigenic mutations in one male patient. The first clinical symptoms of the disease were detected at a median of 48 months of age (range 3-233 months). When individuals with different mutations were compared, there were no differences identified in gender, age of diagnosis, presence of UTI or urolithiasis, eGFR, calcium, or cystine excretion. The most common initial symptoms were urolithiasis in 26 patients (88%) and urinary tract infections in 4 patients (13%). Urological procedures were performed in 18 out of 30 (60%). CONCLUSIONS: The clinical course of cystinuria is similar among patients, regardless of the type of genetic mutation. Most patients require surgery before diagnosis or soon after it. Patients require combined urological and pharmacological treatment for prevention of stone recurrence and renal function preservation.
BACKGROUND:Cystinuria is an inherited disorder that results in increased excretion of cystine in the urine. It accounts for about 1-2% of pediatric kidney stones. In this study, we sought to identify the clinical characteristics of patients with cystinuria in a national cohort. METHODS: This was a retrospective study involving 30 patients from the Polish Registry of Inherited Tubulopathies. Initial data and that from a 6-month follow-up were analyzed. Mutational analysis was performed by targeted Sanger sequencing and, if applicable, MLPA analysis was used to detect large rearrangements. RESULTS:SLC7A9 mutations were detected in 15 children (50%; 10 males, 5 females), SLC3A1 mutations in 14 children (47%; 5 males, 9 females), and bigenic mutations in one male patient. The first clinical symptoms of the disease were detected at a median of 48 months of age (range 3-233 months). When individuals with different mutations were compared, there were no differences identified in gender, age of diagnosis, presence of UTI or urolithiasis, eGFR, calcium, or cystine excretion. The most common initial symptoms were urolithiasis in 26 patients (88%) and urinary tract infections in 4 patients (13%). Urological procedures were performed in 18 out of 30 (60%). CONCLUSIONS: The clinical course of cystinuria is similar among patients, regardless of the type of genetic mutation. Most patients require surgery before diagnosis or soon after it. Patients require combined urological and pharmacological treatment for prevention of stone recurrence and renal function preservation.
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