Clinical and genetic characteristics of the Russian cohort of children with nephropathic cystinosis: single center experience

Introduction. Nephropathic cystinosis (NC) is an extremely rare hereditary disease characterized by the intralysosomal accumulation of cystine crystals caused by mutations in the CTNS gene. NC is the most common cause of Fanconi syndrome in children, which has a poor prognosis without continued pathogenetic therapy, mainly affecting renal function. The aim of the work is to determine the features of the clinical course of NC, the experience of diagnosis and treatment in a multidisciplinary hospital of the federal center. Materials and methods. The retrospective study included 37 NC patients (19 girls, 18 boys) for the period from 2008 to 2024. Results. Manifestations of Fanconi syndrome were noted in all patients; the age of verification of symptoms ranged from 2 to 119 months, the median was 7 [6; 14] months. At the time of diagnosis at the age 8 to 294 months, median 27 [19; 71] months, in 17 (46%) children documented a decrease in eGFR < 60 ml/min/1.73 m2. An extended deletion of 57 thousand pairs of nucleotides was detected in 17 (46%) patients. Renal replacement therapy was initiated in 24 (65%) patients, median age 8.7 [7.7; 11.9] years. Kidney transplantation was performed in 21 patients, median age was 10.2 years (8.8; 13.0), there were no cases of loss of allograft. Pathogenetic cysteamine therapy was initiated in 36 (97.3%) children, range 8 to 174 months, median 33 [23; 82] months, was achieved a decrease the concentration of cystine leukocytes and a decrease in the frequency of extrarenal complications. There were a significant slowdown in the rate of decrease in renal function to CKD stage 3 and stage 5 with early initiation of cysteamine bitatrate and subsequent adherence to therapy. Conclusion. Nephropathic cystinosis is an important problem in Pediatrics due to the extremely late diagnosis and lack of alertness of primary care specialists. Early initiation of supportive and pathogenetic therapy allows improving the condition and development of patients, as well as slowdown the rate of decrease in renal function and extrarenal damage.