Cystinuria is a rare autosomal recessive cause of kidney stones. This metabolic disorder results from mutations in the SLC3A1 and SLC7A9 genes on chromosomes 2 and 19, respectively. Heterozygotes have daily urinary excretion of cystine in excess of 400 mg while homozygotes excrete more than 600 mg.

Prevalence is estimated at 1 in 7000 live births, and as much as 2% of adult nephrolithiasis is attributable to cystine stones. In pediatric populations, as much as 5% of stone formation is attributed to cystinuria.

Affected individuals have impaired transtubular reabsorption of dibasic amino acids, including cystine, ornithine, lysine, and arginine, in the proximal tubule. While cystine has low solubility at normal urinary pH, the other dibasic amino acids are quite soluble and consequently do not result in precipitation or stone formation. However, the excessive urinary cystine excretion leads to cystine nephrolithiasis. Clinically, cystine stones manifest in the same way as other forms of nephrolithiasis with hematuria and colicky flank pain radiating to the groin.

Because cystinuria is a more common form of nephrolithiasis in the pediatric population, there should be high clinical suspicion for cystinuria in a patient who presents with a first episode of stones in adolescence or earlier. While stones can present as early as in infancy, particularly in homozygotes, the median age of onset is 12 years of age. Although there is little explanation pathophysiologically, cystinuria appears to result in more frequent symptomatic episodes in men.