Clinical and genotypic features, renal prognosis of orphan tubulopathies with nephrocalcinosis and cystin stones in children

THE AIM : To evaluate clinical and genotypic features, renal prognosis in orphan tubulopathies with nephrocalcinosis and cys- tine calculi in 22 pediatric patients. PATIENTS AND METHODS : The study included 22 patients (from 1 year 4 months to 17 years 11 months) with orphan tubulopathies with nephrocalcinosis (22) and cystinuria, cystine stones (2). Of the 22 probands, there were 14 (63.6 %) boys and 8 (36.4 %) girls. Clinical, biochemical, imaging, and molecular genetic diagnostic methods were used. The severity of chronic kidney disease was stratified according to the K/DOQI classification (2002). RESULTS : A genetic study of 22 children with nephrocalcinosis revealed primary hyperoxaluria of types I, II, III (AGXT, GRHPR, HOGA1) in 5; familial hypomagnesemia with hypercalciuria and nephrocalcinosis (CLDN16) in 5; hypophosphatemic rickets with hypercal- ciuria and nephrocalcinosis (SLC34A3) in 3; Bartter type I syndrome (SLC12A1) in 1 and Bartter syndrome type IV (BSND) in 1, Dent1 disease (CLCN5) in 1, Dent disease 2 (OCRL) in 1, idiopathic infantile hypercalcemia type I (SLC34A1) in 1 and type II (CYP24A1) in 2. Based on the detection of mutations in the SLC3A1 and SLC7A9 genes, 2 probands were diagnosed with type I and non type I cystinuria. The features of gene mutation variants in 22 children with orphan tubulopathies with nephrocalci- nosis and cystinuria, and cystine nodules were identified. A study of kidney function in 22 children over the age of 2 years with nephrocalcinosis and cystinuria revealed CKD C1 with normal glomerular filtration rate (17), CKD C2, C3, C4 (5). A girl with familial hypomagnesemia with hypercalciuria and nephrocalcinosis due to a mutation of the CLDN16 gene, progression CKD of С1 to C4, underwent kidney transplantation at the age of 18 before starting dialysis. CONCLUSION : Features of the clinical phenotype and variants of mutations of genes of orphan tubulopathies with nephrocalcinosis and cystinuria, cystine stones in 22 children were established. Progression of CKD from C1 with normal glomerular filtration rate to C2, C3, C4 was ascertained from 22 in 5 children (25) % with primary hyperoxaluria type1 (1), hypomagnesemia with calciuria and nephrocalcinosis (3), Dent-2 Disease (1). Identification of gene mutations in molecular genetic studies in children with nephrocalcinosis and cys- tinuria establishes a clinical and genetic diagnosis, the pathogenesis of an orphan tubulopathy, and determines personalized management based on individual genetic characteristics.