Metabolic Disorders and Molecular Background of Urolithiasis in Childhood

Urolithiasis in childhood is less frequently observed than in adults, but it still has a considerable morbidity. In contrast to the situation in adults, an infectious or metabolic cause for stone formation is detected in the majority of pediatric patients. The underlying molecular mechanism of urolithiasis has been shown in a number of conditions, and some of them have been discovered in pediatric patients. Mutations of the AGXT-gene (2q37.3) have been found to be responsible for the enzyme defect in primary hyperoxaluria type I, and two of the genes provoking cystinuria have been identified (type I: 2p21, type III: 19q13.1). In both xanthinuria and 2,8 dihydroxyadeninuria mutations of the responsible gene have been discovered. It is very likely that a molecular basis for the different types of hypercalciuria will also be found, like in X-linked hypercalciuric nephropathy with tubular proteinuria (Dent’s disease), or in X-linked recessive nephrolithiasis (Xp11.22). However, the molecular defect does not necessarily predict the clinical course, even in monogenic diseases. Yet in patients with the same disease genotype extreme differences in the disease phenotype have been observed. This review provides current understanding of the metabolic disorders and molecular mechanisms of urolithiasis in childhood.