Infantile nephropathic cystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene that encodes for cystinosin, a lysosomal cystine carrier. With time, cystine accumulation leads to cell dysfunction in various tissues; the kidneys are initially more involved. Most patients are asymptomatic at birth but present in the first or second year of life with failure to thrive, polyuria, dehydration, and/or rickets, which are secondary to the renal Fanconi syndrome. With very few exceptions, all patients have corneal cystine crystals by 18 months of age that can help in recognising the disease. The diagnosis of cystinosis is based on the demonstration of increased intra‐leucocyte cystine levels and of mutations in the CTNS gene (detection rate >95 %). In Northern Europe, 75 % of mutated alleles carry a 57‐kb deletion; all other types of mutations, generally resulting in a complete or severe loss of function of the cystinosin protein, have been described.
In the past decades, the introduction of cysteamine treatment and improvements in dialysis techniques and renal transplantation have considerably improved the prognosis of cystinosis. Cysteamine significantly delays progression to end‐stage renal failure, but cannot prevent it in most cases. The majority of patients live into adulthood, but, when not appropriately treated with cysteamine, develop other symptoms related to cystine accumulation in various tissues. These include retinal degeneration, hypothyroidism, diabetes mellitus, exocrine pancreatic insufficiency, pubertal retardation and gonadal dysfunction, restrictive pulmonary disease, myopathy, neurological deterioration, and liver involvement. Two milder forms of the disease (juvenile cystinosis and ocular cystinosis), caused by hypomorphic mutations of the CTNS gene, have also been reported; these patients present with milder symptoms later in childhood or with isolated corneal cystine depositions during adulthood.
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