Cystinosis is an autosomal recessive disorder caused by pathogenic variants in the gene CTNS. While it is a pan-ethnic disorder, increased prevalence of the disease has been reported in French Canadians from the Saguenay-Lac St. Jean region and Sephardic Jewish individuals from Morocco. Several forms of the disease, which vary in severity, have been identified: the infantile nephropathic form, the juvenile form, and the adult non-nephropathic form. The infantile form is the most severe, with onset during the first year of life. Accumulation of cysteine in the lysosomes results in kidney problems leading to renal failure in childhood if not treated, as well as cysteine crystals in the eyes that cause photophobia and decreased visual acuity. Without treatment, life expectancy is approximately ten years of age; with treatment, patients may survive until middle age. In the juvenile form, the age of onset and the age of renal failure are delayed relative to the infantile form. In the adult non-nephropathic form, ocular manifestations occur without evidence of kidney disease. In this form, life expectancy is not affected. A genotype-phenotype correlation has been observed where patients carrying alleles resulting in total loss of protein function have the infantile form of the disease, and those carrying at least one allele with residual activity are more likely to have a later-onset or non-nephropathic form of cystinosis.
For information about carrier frequency and residual risk, please see the residual risk table.