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Definition, Etiology, Clinical FeaturesTop
Cystinosis is caused by mutations in the CTNS gene (found on chromosome 17), which encodes a lysosomal cystine/proton symporter termed cystinosin. In the absence of a functional cystinosin protein, cystine accumulates and crystallizes in the lysosomal lumen. Like in other tissues, cystine accumulates in the renal tubules and the interstitium, leading to tubular dysfunction and end-stage renal disease (ESRD).
Cystinosis has 3 forms:
1) The infantile form, also called nephropathic, is the most severe and presents at the age of 3 to 6 months, manifesting as Fanconi syndrome (see Proximal (Type 2) Renal Tubular Acidosis); such children develop ESRD by the age of 10 years.
2) The late-onset form, also known as juvenile, occurs usually around the age of 10 years, and the presentation as Fanconi syndrome is less common. Nephrotic range proteinuria can be a presenting feature. Patients develop ESRD around the age of 15 years.
3) The adult-onset form, which is usually a benign form of the disease, may have only ocular manifestations of photophobia or ocular discomfort.
Diagnosis is made by measuring intraleukocyte cystine content, slit-lamp examination of the eye, and/or testing for the CTNS gene sequence.
Recommended therapy following confirmation of the diagnosis is cysteamine, a chaperone protein that allows for effective excretion of cystine from the cells, preventing tissue deposition and damage. This has been shown to preserve renal function and prevent other end-organ manifestations of the disease.
Patients who undergo transplantation for ESRD resulting from cystinosis, as long as they remain on cysteamine thereafter, have a very indolent course of cystinuria with no recurrence.