Cystinosis

What is cystinosis?

Cystinosis is a genetic condition in which an amino acid called cystine builds up within your cells. Too much cystine can damage your cells. It causes crystals to form that accumulate and then cause issues in your organs and tissues. Cystinosis most often affects your kidneys and eyes. It can also damage your brain, muscles, liver, thyroid, pancreas and testes.

The condition is a rare but serious disease that has a lifelong impact. Prompt diagnosis and treatment can slow the development and progression of the disease. Even with treatment, most people will develop end-stage kidney disease (kidney failure) and require kidney transplants.

What are the different types of cystinosis?

There are three main types of cystinosis. They differ depending on when your symptoms first appeared (age of onset) and the severity of your symptoms.

Nephropathic cystinosis

Nephropathic cystinosis is also called infantile or early-onset cystinosis. It’s the most common form, affecting about 95% of people with the condition. It’s also the most severe form of the disease.

With nephropathic cystinosis, infants develop a type of kidney damage called renal Fanconi syndrome. With this condition, minerals and other nutrients aren’t absorbed into the bloodstream properly. Instead, they’re lost through pee (urine). This loss of nutrients causes growth delays, soft bowed bones (rickets) and many other debilitating symptoms.

By age 2, cystine crystals may form in the corneas of a child’s eyes. The buildup of these crystals can eventually cause an excess sensitivity to light called photophobia. This can cause intense eye pain and discomfort. Children with nephropathic cystinosis will ultimately require a kidney transplant. If left untreated, complete kidney failure will occur by age 10. Children who receive treatment can often survive at least into adulthood with a good quality of life.

Intermediate cystinosis

Intermediate cystinosis is also called adolescent, juvenile or late-onset cystinosis. The signs and symptoms of this type of cystinosis are the same as infantile cystinosis. However, they develop later in childhood or adolescence. The symptoms may be less severe and develop more slowly.

People with intermediate cystinosis will eventually need a kidney transplant. If left untreated, complete kidney failure will occur by their mid-teens to mid-20s.

Non-nephropathic

Non-nephropathic is also called benign or ocular cystinosis. This type of cystinosis affects your eyes only. Cystine crystals in your corneas cause light sensitivity (photophobia). But most people with this type of cystinosis don’t develop kidney damage or experience other symptoms of the disease.

The age at which non-nephropathic cystinosis is diagnosed varies because of the absence of symptoms. But it usually affects middle-aged adults.

Who does cystinosis affect?

Cystinosis is a genetic condition that can affect anyone. The disease is inherited in an autosomal recessive pattern, which means both biological parents must pass on a copy of the mutated gene. If both parents are carriers of the mutated gene, there’s a 1 in 4 (25%) chance they’ll have a child with cystinosis.

How common is cystinosis?

Cystinosis is a rare condition. It occurs in about 1 in 100,000 to 200,000 births worldwide.

How does cystinosis affect my body?

Cystinosis is a type of lysosomal storage disorder. Lysosomes are areas in your cells that break down nutrients, including carbohydrates, proteins and fats. Some proteins are enzymes that absorb these nutrients for your body to use. Other proteins are transporters. They transport the leftovers (such as cystine) out of the lysosomes.

If you lack such a transporter, cystine can accumulate in the lysosomes of your cells. Cystine forms crystals in your cells and slowly damages your organs.

What are the symptoms of cystinosis?

Cystinosis symptoms and severity vary based on the age of onset and diagnosis.

Nephropathic cystinosis symptoms typically appear between the ages of 6 and 18 months as signs of kidney damage develop. These symptoms may include:

• Excessive thirst (polydipsia).
• Excessive urination (polyuria).
• Electrolyte imbalances.
• Vomiting.
• Dehydration.
• Fever.

Other symptoms may include:

• Rickets.
• Growth delay/failure to thrive.
• Scarred or cloudy corneas.
• Light sensitivity (photophobia).
• Vision loss.
• Difficulty swallowing (dysphagia).

The symptoms of intermediate cystinosis are the same as infantile cystinosis. However, they appear later in childhood or during adolescence and they tend to be less severe. Other common symptoms of late-onset cystinosis may include:

• Fatigue.
• Muscle weakness.
• Myopathy.
• Short stature.
• Delayed puberty.
• Infertility.

Ocular cystinosis affects the corneas of your eyes only, and light sensitivity is typically the only sign of the condition. No kidney-related symptoms will develop.

What causes cystinosis?

Genetic mutations in the CTNS gene cause cystinosis. The CTNS gene tells your body how to encode for a protein called cystinosin. Cystinosin is a transporter protein — it’s responsible for transporting the amino acid cystine out of the lysosomes. Lysosomes are compartments in the cells that break down minerals and other nutrients.

A mutation in the CTNS gene causes a defect in the cystinosin. When there’s a defect, cystine can’t get out of the lysosomes and it begins to build up. Crystals form and accumulate which causes damage to the cells in your organs.

Cystinosis is inherited in an autosomal recessive pattern. This means both biological parents carry a copy of the mutated gene, but they usually don’t show symptoms. Both parents have to pass on a copy of the mutated gene for their child to inherit the condition.

How is cystinosis diagnosed?

Your healthcare provider will ask about your symptoms and medical history. They’ll perform a physical exam and request a number of tests to diagnose your condition.

What tests will be done to diagnose cystinosis?

Your healthcare provider may request the following tests to diagnose cystinosis:

• Blood test: A lab technician will remove a sample of your blood to check for cystine levels in your white blood cells.
• Genetic testing: A geneticist will look for genetic mutations in your CTNS gene.
• Urinalysis: A urine test can check for the excess loss of minerals, nutrients, electrolytes and amino acids.
• Eye examination: An eye exam can reveal cystine crystals in your corneas. An ophthalmologist will use a microscope called a slit lamp to look at your eyes with high magnification.

If you’re pregnant and you have a family history of cystinosis, you may be eligible for prenatal testing called amniocentesis to find out if your baby will have the condition if you and your partner are determined to be carriers. Your healthcare provider can get a cell sample from the amniotic fluid surrounding the developing fetus to check for cystine levels.

Providers can use another prenatal test called chorionic villus sampling to test for cystinosis. This test examines cells found on the chorionic villi of the placenta.

How is cystinosis treated?

Cysteamine

The first line of treatment for cystinosis is a medication called cysteamine. Cysteamine is a cystine-depleting agent. That means it works to lower the levels of cystine in the cells in your body.

When used early, cysteamine can slow the development and progression of kidney damage. It has significantly delayed the need for kidney transplantation. Some children have been able to delay the need for a kidney transplant until adulthood. Cysteamine also improves the growth of children with the disease.

Cysteamine is available in two forms: Cystagon™ and Procysbi™. You need to take Cystagon every six hours to be effective. Procysbi, which is intended for people aged 6 and older, has a delayed-release coating, so you can take it every 12 hours.

Standard cysteamine doesn’t treat cystine crystals in your corneas. For that, there are two U.S. Food and Drug Administration (FDA)-approved cysteamine eye drops: Cystaran™ and Cystadrops™. These drops need to be given approximately every hour while awake. They work to dissolve corneal crystals and relieve light sensitivity.

Other treatments

Children with cystinosis will need other treatments depending on their symptoms. Fanconi syndrome treatment includes:

• Consuming lots of fluids and electrolytes to prevent excessive loss of water.
• Medications to maintain a normal electrolyte balance.
• Medications to correct the defective absorption of phosphate into their kidneys.

Other treatments for cystinosis may include:

• Growth hormone therapy.
• Insulin to treat insulin-dependent diabetes.
• Testosterone to treat people with underactive testicular function (hypogonadism).
• Speech and language therapy.
• Genetic counseling.

Some children with feeding difficulties may require a feeding tube (gastronomy tube). This tube is used to ensure proper nutrition and medication administration.

Treatment for ocular cystinosis may also include:

• Avoiding bright lights.
• Wearing sunglasses.
• Keeping your eyes lubricated.
• In rare cases, a corneal transplant may be necessary.

Kidney transplantation

Despite early diagnosis and treatment, people with nephropathic and intermediate cystinosis will eventually develop kidney failure. Your healthcare provider may first treat kidney failure with dialysis. A dialysis machine performs some of the functions of your kidneys. It filters waste from your blood and helps maintain the correct levels of certain chemicals in your body. However, kidney failure isn’t reversible and you’ll eventually require a kidney transplant.

Kidney transplants have worked very well for people with cystinosis. Cystine doesn’t collect in a donated kidney. However, cystine may still build up in other organs in your body. For this reason, you’ll still need to take medication for life.

Complications/side effects of the treatment

The medication cysteamine smells foul and has an unpleasant taste. Because of this, some people may experience nausea, vomiting and heartburn while taking the medication. Cysteamine may also cause excess production of stomach acid. Some people take proton pump inhibitors to reduce stomach acid production. This can help improve their gastrointestinal symptoms. Cysteamine may also cause bad breath (halitosis) and a bad sweat odor.

How can I prevent cystinosis?

You can’t prevent cystinosis because it’s a genetic condition. If you’re pregnant or planning to become pregnant, you may consider genetic testing to learn about your risk of having a baby with the condition.

What is the life expectancy of someone with cystinosis?

At one point in time, nephropathic cystinosis was fatal in young children. Today, with the development of cysteamine and advancements in kidney transplantation, the life expectancy for people with cystinosis reaches far into adulthood. Some people live beyond 50 years of age.

What can I expect if I have cystinosis?

Early diagnosis of cystinosis is vital. You can slow the progression of the disease with proper treatment. Without treatment, children with cystinosis will develop kidney failure by the age of 10. Even with treatment, many children develop kidney failure in later childhood or adolescence. This will require dialysis and eventually kidney transplantation.

If you’re taking cysteamine, you should continue to use it throughout your life. Research shows it can prevent many late complications of cystinosis that don’t involve your kidneys.

A note from Cleveland Clinic

Cystinosis is a genetic condition that can cause a range of symptoms. With early diagnosis and prompt treatment, you can slow the progression of the disease. What was once a terminal condition in young children is now treatable with medication. Even with medication, people with cystinosis will eventually go into kidney failure and require a kidney transplant. However, people with the condition still live well into adulthood.