landscape image doctor talking to child

About Cystinosis

landscape image doctor talking to child

About Cystinosis

landscape image doctor talking to child


Cystinosis Overview

Cystinosis is a rare but serious multi-system genetic disorder that initially manifests in the kidneys during infancy and early childhood as renal Fanconi syndrome.1 A defect in the transport protein cystinosin causes free cystine to accumulate in the body, eventually forming crystals within bodily tissues.

Cystinosis is classified as a lysosomal storage disease and involves multiple organ systems.2 It is potentially sight-threatening.

Normal Lysosome

animation of normal lysosome disposal of cystine

Cystinotic Lysosome

animation of cystine crystal accumulation

The most common form of cystinosis is caused by a deletion on the 57-kb segment of the CTNS gene, but over 100 molecular variants exist.2-4 As with other rare diseases, the complete diagnosis and detection of cystinosis is under-ascertained, leading to a delay in recognition.3 Severe (infantile) cases have severe mutations on both copies of the CTNS gene, while other patients may be heterozygous for the severe mutation. This variance is responsible for cystinosis presentations that are milder and/or late onset.

Clinically Recognized Phenotypes and Their Prevalence

pie chart showing proportion of patients with types of cystinosis
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Infantile (classic) nephropathic cystinosis

  • Accounts for 95% of reported cases2,3
  • Incidence at 1 per 100,000/200,000 live births worldwide2
  • Approximately 600 affected children and adults in the U.S.5
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Juvenile/late-onset (intermediate) nephropathic cystinosis

  • Precise incidence unknown
  • Same organ system involvement as nephropathic cystinosis, but with a slower progression of disease3
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Non-nephropathic/ocular (benign) cystinosis

  • Precise incidence unknown
  • Characterized only by corneal crystal accumulation with no renal component or organ involvement whatsoever2
dna helix floating above doctor's hand
eye cystinosis pie chart and doctor with dna helix above hand
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Nonrenal Complications of Cystinosis

Complications may include6:
Click on the blue buttons to view complications
- Photophobia (due to corneal involvement)
- Retinal blindness
- Benign intracranial hypertension
- Central nervous system impairment
- Cerebral calcifications
- Corneal crystals
- Swallowing dysfunction
- Hypothyroidism
- Pulmonary dysfunction
- Diabetes mellitus – requiring insulin therapy
- Pancreatic exocrine insufficiency
- Nodular regenerating hyperplasia of the liver
- Vacuolar myopathy
- Male hypogonadism
- Vascular calcifications
- Hypercholesterolemia

Nonrenal Complications
of Cystinosis

Complications may include6:
Click on the blue buttons to view complications

Ocular Complications of Cystinosis

While a cystinosis patient’s systemic therapy can help prevent crystal accumulation in the eye’s posterior segment and prevent complications there, including retinal damage, there is no vascular supply to the cornea to deliver the drug.5,7,8

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The cornea is left vulnerable to accumulating crystals, necessitating the use of a topical therapy.5,7,8 In untreated or undertreated cases, corneal complications can be severe8:

Band keratopathy
Corneal scarring
Peripheral corneal neovascularization
Posterior synechiae (adherence of the iris to the lens)
Pupillary block with secondary glaucoma
diagram of eye

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The need for a "whole-eye" approach to cystinosis that encompasses adherence to both systemic and topical medication is clear.

Diagnostic Methods and Criteria

Multiple methods exist for diagnosing cystinosis:

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Systemic Diagnosis

Diagnosis of nephropathic cystinosis (whether infantile or juvenile) can be made by measuring leukocyte cystine content (LCC).3

  • In unaffected persons, concentration is less than 0.2 nmol of half-cystine per mg of protein
  • In nephropathic cystinosis patients, values exceed 2.0 nmol per mg of protein

Ocular Diagnosis

Imaging of the corneas may show crystal accumulation in affected patients and is a suitable diagnostic indicator for ocular cystinosis.5

  • Slit-lamp photography is often used, although this is not a reliable method in infants younger than one year of age3
  • Other ophthalmologic diagnostic tools are available

Molecular Diagnosis

Molecular diagnosis can be done in affected individuals to confirm the presence of the defective CTNS gene. This can be accomplished through prenatal chorionic villi sampling or DNA testing on cultured fibroblasts obtained from a skin biopsy.9

  • Compound heterozygous or homozygous mutations should be found
  • Genetic testing of both the patient and the patient’s family is recommended