Genetic Causes of Kidney Stones: Cystinuria, Primary Hyperoxaluria, Dent's Disease, and APRT Deficiency

The characterization of numerous rare single gene defects associated with nephrolithiasis and/or nephrocalcinosis has advanced our understanding of molecular pathways leading to stone formation. Collectively these monogenic disorders only account for approximately 2% of kidney stones in adults and 10% of childhood stones. Lack of awareness of these rare disorders by physicians or absence of characteristic clinical features that distinguish them from the common type of kidney stones frequently results in unacceptable delays in diagnosis and treatment. A genetic disorder should always be considered during evaluation of kidney stones in children and in unusual adult cases. Important clues that should alert the clinician to a genetic cause of nephrolithiasis will be reviewed along with several of the most common or best characterized single gene disorders, cystinuria, primary hyperoxaluria, Dent's disease, and adenine phosphoribosyltransferase deficiency.