PATIENTs AND FAMILIES Understanding Cystinosis

Cystinosis at a glance

  • Affects approximately 1 in 100,000 to 1 in 200,000 people1
  • Caused by defect in the CTNS gene
  • Characterized by toxic buildup of the amino acid cystine, which then crystalizes in the lysosomes, significantly reducing their ability to function
Cystinosis symptoms
  • Chronic kidney disease, kidney failure and other kidney disorders including:
    • Renal Fanconi syndrome, a disorder in which certain substances normally absorbed into the bloodstream by the kidneys are instead released into the urine
    • Proteinuria, or abnormally high levels of protein in the urine
  • Accumulation of cystine in the cornea, photophobia (light sensitivity), involuntary eyelid closures
  • Muscular disorders such as myopathy (improper functioning of muscle fibers, leading to muscular weakness), hypotonia (decreased muscle tone), tremors, or difficulty swallowing
  • Neurodevelopmental issues, including speech and walking delays and cognitive impairment
  • Softening/weakening of bones, bone pain, rickets, long bone deformation, delayed growth
  • Endocrine disorders including hypothyroidism (underactive thyroid gland), insulin resistance, diabetes and infertility
Treating cystinosis

The only treatment for cystinosis is cysteamine, which is typically taken orally and as eye drops. This treatment helps to lower the amount of cystine in the cells, slowing but not halting the overall progression of the disease. Even while on cysteamine therapy, people living with cystinosis often require kidney transplants.

People with cystinosis face a highly challenging treatment regimen. They may take dozens of pills a day, on a strict schedule around the clock, and use eye drops every few waking hours. Unfortunately, cysteamine has a bad taste and smell and can lead to unpleasant side effects, and people living with cystinosis often find it difficult to adhere to the treatment regimen.

The advent of cysteamine therapy and improvements in kidney transplants have extended life expectancy into adulthood for people with cystinosis.2 Yet even on the standard of care, people with cystinosis have a significantly shortened life expectancy and may experience debilitating symptoms that reduce their quality of life.

At AVROBIO, we are developing a new approach that could halt progression or reverse damage caused by cystinosis with a single dose.

Learn about our investigational gene therapy.

Learn about our clinical trial
in cystinosis.

What causes cystinosis?

Cystinosis is caused by a mutation on a single gene known as CTNS.

The CTNS gene provides the instructional code for making cystinosin protein, which transports cystine out of lysosomes. When the gene is mutated, cystine builds up in the lysosomes. The accumulating cystine forms crystals, which can cause tissue and organ damage.3

Normal Lysosome vs. Cystinosis lysosome

Normal Lysosome vs. Cystinosis lysosome

There are several forms of cystinosis

Symptoms vary widely depending on the age of onset and severity of the disease:

  • Infantile nephropathic cystinosis is the most common and severe form of cystinosis; the kidneys and eyes are typically substantially impacted.4
  • Juvenile or late-onset nephropathic cystinosis is usually diagnosed in childhood or adolescence and leads to kidney disease and muscle atrophy.5
  • Ocular (non-nephropathic) cystinosis involves the eyes but not the kidneys and is often diagnosed in adulthood.6,7
How is cystinosis inherited?

Healthy people have two working copies of the CTNS gene that provide the instructional code for making the lysosomal cystinosin transport protein.

When one of those copies is faulty, the individual is considered a “carrier” for cystinosis but will not develop it. When a carrier has a child, he or she has a 50/50 chance of passing the faulty gene to the child.

A child who inherits two faulty genes may develop cystinosis. Males and females are equally affected.

Pompe inheritance chart and Cystinosis inheritance chartPompe inheritance chart and Cystinosis inheritance chart

*These links are provided for informational purposes only. AVROBIO is not affiliated with any of these institutions and is not responsible for any of the content on their websites.

Learn about our cystinosis trial

A Phase 1/2 study to evaluate the safety and efficacy of AVROBIO's investigational gene therapy for cystinosis (AVR-RD-04) is currently enrolling patients at a clinical site in San Diego, Calif. This study is sponsored by our academic collaborators at the University of California, San Diego. At this time, enrollment is restricted to adults who are currently being treated with cysteamine. There are additional eligibility criteria.

Learn more

References
  1. Nesterova G, et al. Cystinosis. GeneReviews. Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle. (2016).
  2. National Organization for Rare Disorders (NORD). Rare Disease Database: Cystinosis. https://rarediseases.org/rare-diseases/cystinosis/. Accessed December 23, 2019.
  3. Wilmer MJ, et al. Cystinosis: practical tools for diagnosis and treatment. Pediatr Nephrol. 2011;26(2):205–215.
  4. Emma F, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant. 2014;Suppl 4:iv87-94.
  5. Nesterova G, et al. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2013; 28:51–59.
  6. Gahl WA, et al. Cystinosis. N Engl J Med. 2002;347:111–121.
  7. National Institutes of Health. Genetics Home Reference: Cystinosis. https://ghr.nlm.nih.gov/condition/cystinosis. Accessed November 20, 2019.

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