Clinical Information

Cystinuria is an inborn error of metabolism resulting from poor absorption and reabsorption of the amino acid cystine in the intestine and in the kidney. This leads to an accumulation of poorly soluble cystine in the urine and results in the production of kidney stones (urolithiasis). Symptoms may include acute episodes of abdominal or lower back pain, presence of blood in the urine (hematuria), and recurrent episodes of kidney stones may result in frequent urinary tract infections, which may ultimately result in renal insufficiency. The combined incidence of cystinuria has been estimated to be 1 in 7,000.

Cystinuria can be classified into 3 subtypes based on the excretion of amino acids in the urine of heterozygotes (parents or children of affected individuals). Heterozygotes of type I excrete normal amounts of cystine, while those with types II and III present with slight to moderate excretion of cystine and other amino acids (lysine, arginine, and ornithine). All 3 subtypes are caused by mutations in only 2 genes, SLC3A1 on chromosome 2p and SLC7A9 on chromosome 19q. A new classification system has been proposed to distinguish the various forms of cystinuria: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to 1 mutation in each SLC3A1 and SLC7A9.