Cystine Stones

Cystine stones occur in subjects carrying two autosomal mutant alleles resulting in excessive excretion of cystine, ornithine, arginine and lysine – hence the condition cystinuria. About 1:15–25 000 NSW neonates have been found to have cystinuria, with a gene frequency in Australia calculated to be about 1:4000 individuals. Since these studies were published, the mutant alleles have been identified and possibly there have been changes in Australian genetic demographics. There are three clinical subtypes. Type I heterozygotes excrete normal amounts of cystine, types II and III heterozygotes have higher than normal amounts but less than in the homozygote stone formers. Mixtures, e.g. type I/ III, can occur. Type I/I ‘classical cystinuria’ is due to mutations in the SCL3A1 gene on chromosome 2. Homozygotes usually have two different mutations of the SCL3A1 gene. Mutations in the SCL 7A9 gene on chromosome 9 are associated with non-type I disease. The specific gene frequencies in the Australian population have not been reported. For simplicity, in these guidelines, patients who have two alleles with mutations of any of the genes will be referred to as ‘homozygotes’.