Cystinosis

Cystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene that encodes for cystinosin, a lysosomal cystine/H⁺ symporter. The disease causes progressive accumulation of cystine in virtually all tissues. In the most frequent and severe form, termed nephropathic infantile cystinosis, kidney involvement is responsible for the initial symptoms, with patients presenting in the first year of life with symptoms related to renal Fanconi syndrome. Cystine corneal crystals are present in all patients by the age of 2 years. The diagnosis is based on the detection of increased leucocyte cystine levels and the demonstration of mutations in the CTNS gene. Cysteamine was introduced in the 1980s for the treatment of cystinosis. Cysteamine has considerably improved the prognosis of the disease and delays progression to end-stage kidney disease by approximately 10 years. If not appropriately treated, patients rapidly develop other symptoms, including retinal degeneration, hypothyroidism, diabetes mellitus, exocrine pancreatic insufficiency, pubertal retardation, gonadal dysfunction, restrictive pulmonary disease, myopathy, neurological deterioration, and liver involvement. Two milder forms of the disease, namely juvenile cystinosis and ocular cystinosis, have also been described. These patients present with milder symptoms later in childhood or with isolated corneal cystine depositions, respectively.