Prospective analysis and classification of patients with cystinuria identified in a newborn screening program.

Patients who inherit mutant cystinuria genes excrete high concentrations of cystine, ornithine, arginine, and lysine in the urine. At least three variants of cystinuria can be distinguished in heterozygotes. To determine whether certain combinations of mutant genes are more disadvantageous than others, we analyzed amino acid excretion in families of 17 probands with cystinuria identified by the Quebec neonatal screening program. Parents of the probands were classified into the three known phenotypes by calculating the sum of cystine, ornithine, arginine, and lysine excretion. Although parents of type I/I homozygotes excreted amounts of cystine in the normal range, their offspring excreted significantly greater amounts of urinary cystine than did children who have type I/III genetic compounds. This observation suggests that types I and III cystinuria mutations might involve two distinct genetic loci. Children with type I/I homozygous cystinuria often excrete cystine at levels greater than the theoretic solubility limit and may be at greatest risk for nephrolithiasis. We outline an approach to monitoring children with cystinuria who come to medical attention before formation of cystine stones.