What is Cystinosis?

Cystinosis symptoms

• Cystinosis is a rare autosomal recessive lysosomal storage disorder resulting in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. 

• Cystinosis affects approximately 1 in 100,000 to 1 in 200,000 people and an estimated 2,000 people worldwide. 

• It is caused by a defect in the CTNS gene and cystine when an amino acid builds up in the lysosomes. The accumulating cystine forms cystine crystals within almost all tissues and organs in the body, subsequently affecting their function. 

• Renal symptoms typically develop in the first few months of life with extra-renal manifestations becoming apparent over the next 10–20 years. 

• Cystine crystals have recently been shown to activate cells of the immune system potentially triggering a chronic inflammatory process, apoptosis and oxidative stress within affected cells. 

• Cystinosis treatment can slow down and delay the effects but not halt the overall progression of the disease. 

• Cystinosis remains incurable at this stage.

Defects in the CTNS gene prevent cystinosin from working properly or from being produced in the right amounts.

What causes Cystinosis?

Cystinosis is caused by a genetic defect in the CTNS gene, which tells the body how to build an essential transporter protein called cystinosin. This defect is usually a deletion of a specific portion of the gene—the 57-kb segment. However, other types of defects on the CTNS gene or varied levels of deletion exist. These variations are responsible for how the disease can behave differently in different people. 

The CTNS gene tells the body instructions for making cystinosin protein, which transports cystine out of lysosomes. When the gene is mutated (a genetic defect) the cystine builds up in the lysosomes and the accumulating cystine forms crystals in all of the cells which causes organ and tissue damage throughout the body.

Cystinosis affects nearly every cell and organ in the body

There are three forms of Cystinosis

Australian Cystinosis Foundation_Info Graphic-06@2x (1)

Infantile Nephropathic Cystinosis

Other terms: Infantile cystinosis, classic cystinosis

The most frequent (95%) and severe presentation and includes renal Fanconi syndrome.

Australian Cystinosis Foundation_Info Graphic-06@2x2

Intermediate Cystinosis

Other terms: Juvenile cystinosis, late-onset cystinosis

Affects a small group of patients and characteristically can present with proteinuria and mild or absent tubulopathy. It has a slower rate of progression but can still progress to kidney failure.

Australian Cystinosis Foundation_Info Graphic-06@2x1

Ocular Non-nephropathic Cystinosis

Other terms: Ocular cystinosis, benign cystinosis, adult cystinosis

Rarely presents before adulthood. Typically involves the presentation of photophobia due to corneal accumulation of cystine however, the kidneys may still be affected.

Cystinosis symptoms

• Kidney damage and end-stage renal disease.

• Fanconi syndrome, a disorder in which substances such as electrolytes and minerals normally absorbed into the bloodstream by the kidneys are instead released into the urine (Polyuria). 

• Proteinuria or abnormally high levels of protein in the urine. 

• Accumulation of cystine in the cornea, photophobia (light sensitivity) or involuntary eyelid closures. 

• Muscular disorders such as myopathy, 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, hypogonadism, delayed puberty, diabetes and male infertility.

What is Fanconi syndrome?

Over time Cystinosis causes damage to the kidneys, affecting the proximal tubules and their ability to reabsorb electrolytes and other substances. This damage to the proximal tubules makes the kidneys increasingly unable to absorb the essential nutrients and filter out the body’s waste. Essential and critical nutrients that would normally be absorbed are instead passed through the kidneys and are eliminated in the urine.
Fanconi syndrome is often the first sign of Cystinosis and can lead to a diagnosis.


Symptoms of Fanconi syndrome can include:

• Excessive urination (Polyuria)
• Excessive thirst (Polydipsia)
• Dehydration
• Reduced appetite
• Fatigue
• Muscle weakness
• Weight loss
• Slow growth
• Softening or weakening of bones (rickets)

Eventually, the damage caused by Cystinosis causes the kidneys to fail completely which can be treated only with dialysis and ultimately a kidney transplant.

While a transplanted kidney may not be affected by Cystinosis the cystine-depleting therapy still needs to be taken even after the transplant to continue to help delay or reduce the cystine damage to other organs.

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. The CTNS gene is found on chromosome 17 and over 140 pathogenic mutations have been reported within the gene. The most common mutation is the 57 kb deletion which includes exons 1-9 and part of exon 10 of CTNS. Homozygosity for the 57 kb deletion is very common, accounting for 46% to 75% of mutations in people of Northern European ancestry.

How is Cystinosis diagnosed?

There are three main diagnostic modalities for Cystinosis.

The current standard is the detection of elevated cystine levels in the blood cells via a white cell cystine test (used both for diagnosis of Cystinosis and the monitoring of levels whilst on cysteamine therapy).

Genetic testing of the CTNS gene is a well-established technique revealing 95% of disease causing mutations.

The third option is the detection of cystine crystals found on the cornea by a slit lamp examination. A thorough diagnosis of Cystinosis is usually based on two tests, usually the white blood cell cystine test along with genetic testing of the CTNS gene.

Treating Cystinosis

Early diagnosis and effective cystine depletion treatment is essential for improving the overall prognosis and quality of life of patients with Cystinosis. 

The severity of kidney dysfunction and multiple organ involvement as a consequence of the increased levels of cystine highlight the necessity of accurate monitoring of cystine levels to guarantee the effective treatment of the disease. 

Cystine depletion treatment (cysteamine therapy) is currently the only available treatment and should be administered as soon as possible after diagnosis to significantly slow the progression of renal and multiple organ damage.

Cystine depletion treatment

The only cystine depletion treatment for Cystinosis is known as cysteamine therapy which is available in a capsule called CYSTAGON® (cysteamine bitartrate) and taken every 6 hours or PROCYSBI® (cysteamine bitartrate) a delayed-release capsule taken every 12 hours. PROCYSBI® is not available here in Australia.

Cysteamine eye drops are used in conjunction with the oral cystine depletion treatment to treat the cystine crystal build-up in the eyes. The eye drops are required to be administered every four hours as the oral cystine depletion treatment is not able to reach the eyes as there is no blood supply to the cornea to deliver the treatment.

The oral and ocular cystine depletion treatments help to lower the amount of cystine in the cells which helps slow down and delay but not halt the overall progression of the disease. Even while on the cystine depletion treatment people with Cystinosis will eventually require a kidney transplant and coordinated clinical multidisciplinary care throughout their life.

It is a daily challenge for those living with Cystinosis to administer over 50 pills a day even late at night eg 1am. Along with dealing with unpleasant side effects such as nausea, vomiting, anorexia, bad breath, a sulphur smell throughout the body, abdominal pain, dyspepsia, constipation, gastroenteritis, duodenitis and gastrointestinal ulceration all of which can lead to treatment adherence issues when managing such a challenging medication regime.

Cysteamine therapy has certainly helped extend the life expectancy of those with Cystinosis into adulthood however people with Cystinosis remain to have a significantly shortened life expectancy and experience daily debilitating symptoms that reduce their quality of life.

What is a cystine level test?

Cystine level testing measures the amount of cystine in white blood cells via a white blood cell test. Testing is the only way to know a person’s cystine level and it’s important to know a person’s cystine level to help work out the correct cysteamine therapy dose and when it needs to be adjusted. The only way to know how well the cysteamine therapy is working is through regular white blood cell cystine level testing.