Genetic and Biochemical Features of the Monogenic Hereditary Kidney Stone Disease

Kidney stone disease (KSD) is a common urological problem. In most cases, this multifactorial pathology develops due to the combination of inherited low-penetrance gene variants and environment factors such as urinary tract infections, unbalanced diet, and gastrointestinal tract diseases with malabsorption. However, some cases of KSD represent monogenic diseases in which mutations are inherited from one or both parents. These hereditary forms of KSD, manifested in childhood, are characterized by multiple, bilateral or recurrent kidney stones and the earlier development of chronic kidney disease. Introduction of methods for exome and gene panels (NGS—Next Generation Sequencing) sequencing, significantly increased the proportion of detectable genetically identifiable hereditary forms of KSD in the group of patients under 18 year old, which exceeded 20%. In this review we have analyzed genetic and biochemical mechanisms of the main hereditary forms of KSD, associated with enzymopathies (primary hyperoxaluria, adenine phosphoribosyltransferase deficiency, phosphoribosylpyrophosphate synthetase superactivity, xanthinuria, Lesch-Nyhan syndrome) and impaired membrane transport (Dent’s disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypophosphatemic urolithiasis, distal tubular acidosis, cystinuria, Bartter’s syndrome). We suggest a comprehensive gene panel for NGS diagnostics of the hereditary KSD. Accurate and timely diagnosis of hereditary forms of urolithiasis makes it possible to identify a pathological germinal mutation and make an accurate diagnosis, to analyze the heterozygous mutation carriage in affected families and evaluate the prognosis of KSD development in family members, as well as to perform personalized management of the patients with KSD.