Cystinosis

Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, which encodes cystinosin, a lysosomal membrane transporter responsible for exporting cystine out of lysosomes. When this transporter is deficient or absent, cystine accumulates within lysosomes throughout the body, forming crystals that progressively damage cells and organs. The disease is also known as cystine storage disease. Three clinical forms are recognized based on severity and age of onset. The most common and severe form is infantile (nephropathic) cystinosis, which typically presents between 6 and 12 months of age with renal Fanconi syndrome — characterized by excessive urinary loss of glucose, amino acids, phosphate, bicarbonate, and other small molecules. Affected children develop failure to thrive, polyuria, polydipsia, dehydration, rickets, and progressive renal insufficiency that, if untreated, leads to end-stage kidney disease by approximately 10 years of age. The intermediate (late-onset or juvenile) form presents later in childhood or adolescence with milder renal disease, while the ocular (non-nephropathic or benign) form is limited primarily to corneal cystine crystal deposition causing photophobia. Beyond the kidneys, cystinosis can affect multiple organ systems over time, including the eyes (corneal crystals, retinopathy), thyroid (hypothyroidism), pancreas (diabetes mellitus), liver, muscles (myopathy and swallowing difficulties), and central nervous system (cerebral atrophy, cognitive difficulties). The cornerstone of treatment is oral cysteamine (Cystagon or the delayed-release formulation Procysbi), which enters lysosomes and reacts with cystine to form a compound that can exit via an alternative transporter, thereby reducing intracellular cystine accumulation. Cysteamine eye drops (Cystadrops) are used to dissolve corneal crystals. Early and consistent treatment with cysteamine has been shown to significantly delay renal deterioration and reduce extra-renal complications. Supportive care includes electrolyte and fluid replacement for Fanconi syndrome, vitamin D and phosphate supplementation for rickets, and renal transplantation when end-stage kidney disease occurs.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Cystinosis