Cystinuria at the turn of the millennium: clinical aspects and new molecular developments

Cystinuria is caused by a defect in a transport molecule in the kidney and small intestine resulting in urinary excretion of cystine and the dibasic amino acids. Traditionally, three types have been recognized, but this classification correlates poorly with the findings of molecular analysis, and a new system is needed. Persons who are homozygous and heterozygous for non-Type I cystinuria can be distinguished by urinary amino acid excretion: the former secrete large amounts of cystine and all three dibasic amino acids, whereas the latter secrete more lysine and cystine than arginine and ornithine. The first gene found that is important in cystine transport is SLC3A1, located on chromosome 2p. More than 40 mutations have been identified, all associated with Type I cystinuria. The gene associated with non-Type I disease maps to chromosome 19, called SLC7A9, encodes a protein that apparently interacts with the product of the SLC3A1 gene. Almost 40 disease-associated mutations have been identified in SLC7A9, and there is some evidence that cystinuria in some patients reflects mutations in both genes. Mutations in other proteins with which the SLC3A1 and SLC7A9 products associated may be responsible for still other cases of cystinuria. Contemporary molecular knowledge has not offered any new treatment for the short term.