Cystinosis: clinical presentation, pathogenesis and treatment.

Nephropathic cystinosis is a rare lysosomal storage disorder caused by mutations in the CTNS gene ncoding the lysosomal cystine transporter cystinosin. Cystinosin deficiency leads to accumulation of cystine in the lysosomes of cells throughout the body and deregulation of endocytosis, trafficking of intracellular vesicles and related cell signalling processes. One of the early features of the disease is renal Fanconi syndrome characterized by polyuria, proteinuria and urinary loss of various solutes. Later in life, extrarenal complications become apparent, and decline of kidney function leads to the development of end-stage renal disease. Modern therapy of the disease is based on treatment with cystine-lowering drug cysteamine, which helps to postpone the disease progression and development of extra-renal pathologies, but offers no cure for the Fanconi syndrome. Besides the improvement of cystine-lowering therapy based on new formulations of cysteamine, further development of therapy is necessary. Some steps forward were done in the recent years, including studies of cell signalling abnormalities in cystinosis and development of stem cell and gene therapy approaches.