Cystinosis is a rare inherited lysosomal storage disorder following the Mendelian inheritance pattern. It is caused by mutations in the CTNS gene that encodes cystinosin, a lysosomal cystine‑proton co-transporter with various functions. This results in an abnormal accumulation of the amino acid cystine within the lysosomes of all body cells and tissues.
There are three clinical presentations of the disease. Nephropathic infantile cystinosis is the most frequent (95% of cases) and severe type, typically diagnosed in the first two years of life due to impaired growth and renal dysfunction. Late-onset (or juvenile) nephropathic cystinosis causes similar signs and symptoms, but presents between the ages of 15 and 25, with no remarkable growth retardation and slower progression. Non-nephropathic (or ocular) cystinosis is characterised only by photophobia resulting from corneal crystal accumulation and usually presents in adult patients.
The most significant signs include proximal tubular Fanconi syndrome, followed by renal glomerular damage and end-stage renal disease (ESRD), as well as hepato-/splenomegaly, muscle wasting, neurological and ocular abnormalities, metabolic disturbances and abnormal laboratory results.
Untreated cystinosis has a 33% mortality rate. The only currently available target-specific treatment of cystinosis is cysteamine that allows cystine to exit lysosomes via the transport system for cationic amino acids and depletes cells of more than 90% of their cystine content. If initiated early in life, long-term treatment improves survival and final body height and weight, while considerably delaying renal dysfunction. Symptomatic treatments are used, e.g., to support kidney function and manage endocrinopathies. Once ESRD occurs, renal allograft is the treatment of choice.
The Epiomic™ database contains a forecast of the prevalent case load for cystinosis in males and females, as well as patient population broken down into the three clinical presentations of the disease.
Complications of cystinosis include retinal blindness, vacuolar myopathy, diabetes mellitus, pancreatic exocrine insufficiency, central nervous system involvement and pulmonary dysfunction.