Clinical Characteristics
Ocular Features: 

Cystinosis is a clinically heterogeneous disorder that has been divided into three allelic forms based on the age of onset and the amount of kidney disease.  Since the three types are caused by mutations in the same CTNS gene they are discussed here as a single entity with emphasis on the similarities and differences.  All three cause significant corneal disease secondary to crystalline cystine deposits.

The early onset and most common form of cystinosis (219800) causes severe photophobia and even corneal erosions from accumulation of refractile cystine crystals which can be seen in the first years of life.  Accumulation of cystine in the retina leads to peripheral pigmentary changes that progress centrally and is present to some degree in all patients by age 7 years.  Mottling of the retinal pigment epithelium is the most common finding but there are often alternating areas of hyperpigmentation and depigmentation as well.  Visual fields may be markedly constricted.  Photoreceptor damage eventually leads to decreased rod and cone responses as recorded by ERG.  Visual acuity ranges from near normal to NLP.

The late-onset juvenile nephropathic (219900) form has a similar corneal profile but the pigmentary retinopathy occurs later than in the infantile disease.

The adult nonnephropathic form (219750) likewise has visible cystine crystals in the cornea.  This disorder should be considered in all healthy adults with a crystalline dystrophy of the cornea.  The pigmentary retinopathy does not occur.

Systemic Features: 

In the more common infantile form of cystinosis, accumulation of cystine leads to dysfunction in many organs.  Nephropathy, hypothyroidism, and growth retardation in the infantile type are major complications.  The kidney disease leads to a Fanconi syndrome type pattern of kidney failure.  Pancreatic insufficiency, ovarian failure, myopathy, and central nervous system signs are often seen.  Patients require renal transplantation, often in the first decade of life.  Slow eating and dysphagia are common.  Heterozygotes may have elevated levels of free cystine in leukocytes.

The later onset juvenile form of cystinosis presents with kidney failure secondary to glomerular damage instead of tubular dysfunction.  The age of diagnosis varies widely, however, anywhere from 2-26 years of age, with end-stage kidney failure occurring generally in the third decade.  Aminoaciduria is usually not present and growth is normal.

The adult-onset or benign type is also uncommon.  Patients with this non-nephropathic type (219750), of course, do not develop kidney disease but have demonstrable cystine deposits in the cornea, buffy coat, and bone marrow.  No proteinuria or amino aciduria is detectable.


Cystinosis is an autosomal recessive disease that is found in individuals homozygous for mutations in the CTNS gene (17p13) that encodes cystinosin.  The most common mutation among Caucasians of European descent is a 57-kb deletion which sometimes includes contiguous and regulatory genes.  Other sequence variants have also been found.  High cystine levels can be demonstrated in leucocytes of heterozygotes, at least in the infantile form.   A large number of mutations, both homozygous and compound heterozygous, have been found .  The accumulation of cystine seems to result from impaired cystine transport across the lysosomal membrane and it has been suggested that the severity of disease depends on the amount of functional cystinosin produced by various mutations in the CTNS gene.

Treatment Options: 

Topical cysteamine eye drops can dramatically reduce the number of cornea crystals and improve symptoms such as photophobia and visual acuity.  Oral administration of the same drug can be beneficial for systemic disease as well, especially if initiated before the age of two years.  It can also reduce the frequency and severity of posterior segment disease with the most benefit occurring in those who begin the drug early in life.  Improved kidney function and quality of life may be dramatic.

The chronic nature and multisystem involvement require lifelong monitoring of ocular and systemic disease.

Article Title: 


Tsilou ET, Rubin BI, Reed G, Caruso RC, Iwata F, Balog J, Gahl WA, Kaiser-Kupfer MI. Nephropathic cystinosis: posterior segment manifestations and effects of cysteamine therapy. Ophthalmology. 2006 Jun;113(6):1002-9.

PubMedID: 16603246

Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser-Kupfer MI. Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol Genet Metab. 2000 Sep-Oct;71(1-2):100-20. Review.

PubMedID: 11001803

Anikster Y, Shotelersuk V, Gahl WA. CTNS mutations in patients with cystinosis. Hum Mutat. 1999;14(6):454-8. Review.

PubMedID: 10571941