Cystinosis: Symptoms, Types, Treatment Options, and Long-Term Outlook

Cystinosis is a rare, inherited metabolic disorder. It affects how the body processes an amino acid called cystine. In people with cystinosis, cystine is collected and stored in the cells and isn’t properly transported outside of the cells. Over time, this accumulation forms crystals that damage tissues and organs throughout the body.

Cystinosis is a rare but serious condition. It can be life-threatening if it is not caught early and treated promptly, and there is no way to remove it. However, because of developments in cystine-depleting treatment, many patients can now be treated to live long, healthy adult lives.

What Is Cystinosis?
Cystinosis is a lysosomal storage disorder. This type of disorder occurs when there is a mutation that keeps cystine, a small amino acid, from exiting the lysosome. Lysosomes are like the digestive bags for cells that break down food and are found throughout the body. Excess cystine builds up inside lysosomes and eventually crystallizes, causing damage to the following organs:
Eyes
Liver
Brain
Kidneys
Muscles
Thyroid
Pancreas
Reproductive organs

The kidneys and eyes are usually affected initially, which is why cystinosis is often identified through kidney complications in infancy or early childhood.

Types of Cystinosis:
There are mainly three types of cystinosis. They may differ based on when symptoms appeared and how severe your symptoms are.

Nephropathic Cystinosis (Infantile Form):
Nephropathic cystinosis is the most common and most severe type of cystinosis. It accounts for nearly 95% of cases. It usually occurs in infants between 6 and 18 months of age. This form results in a disorder known as renal Fanconi syndrome. In this, the kidneys fail to reabsorb essential nutrients, minerals, and electrolytes. This causes the body to lose them through urination, resulting in severe problems.

Common features include:
Excessive thirst and urination
Dehydration and electrolyte imbalance
Poor weight gain and delayed growth
Weak bones and rickets
Worsening damage to the kidneys

Untreated children with nephropathic cystinosis get end-stage kidney disease very early. Currently, early intervention using pediatric renal lysosomal disorder treatment and cystine-lowering therapy have significantly delayed kidney failure for a lot of these patients.

Intermediate (Juvenile) Cystinosis:
Intermediate cystinosis, sometimes also called adolescent or late-onset cystinosis. It develops later in childhood or during teenage years. Symptoms are like those in cystinosis nephropathy but progress more slowly.

Patients may experience:
Fatigue
Muscle weakness
Delayed puberty
Short stature
Gradual kidney dysfunction

Intermediate cystinosis is less aggressive, but if left untreated, it can still lead to kidney failure, often during late adolescence or early adulthood.

Ocular Cystinosis:
Ocular cystinosis is the least severe type, and it mainly affects the eyes. In this type, the cornea (the front part of the eye) gets cystine (an amino acid) crystals, which can cause discomfort and make it hard for the person to see in bright light.
Unlike the other types of cystinosis, ocular cystinosis does not cause any problems with the kidneys. Many people with this type of cystinosis are diagnosed when they are olde,r and this can be found when a person gets a regular eye check-up.

A key feature is the presence of a corneal cystine crystal, which causes:
Irritation in the eyes
Severe sensitivity to light (photophobia)
Visual discomfort

Who Is Affected by Cystinosis?
People from all ethnic backgrounds are affected by Cystinosis. It is inherited in an autosomal recessive pattern, meaning a child needs to receive one mutated gene from each parent in order to develop the condition.
If both parents are carriers of the mutated gene:
The child has a 25% chance of having cystinosis.
There is a 50% chance the child will just be a carrier.
There is a 25% chance the child will inherit normal (non mutated) genes from both parents.

Globally, cystinosis occurs in approximately 1 in 100,000 to 200,000 births. This makes it a rare condition.

Symptoms and Causes:
What are the symptoms of cystinosis?
The severity of symptoms is largely dependent on the age of the individual at which the symptoms present and the age at which the individual is properly diagnosed.
Nephropathic cystinosis symptoms typically present between the ages of 6-18 months. This is generally when the first signs of kidney damage are present. Symptoms include:
Fever
Electrolyte imbalances.
Vomiting.
Dehydration.
Excessive thirst (polydipsia).
Excessive urination (polyuria).

Other symptoms may include:
Rickets.
Scarred or cloudy corneas.
Growth delay/failure to thrive.
Light sensitivity (photophobia).
Vision loss.
Difficulty swallowing (dysphagia).

The intermediate cystinosis symptoms are the same as those of infantile cystinosis. These symptoms present later in childhood or during adolescence, and are generally less severe. Other symptoms associated with late-onset cystinosis include:
Fatigue.
Myopathy.
Short stature.
Delayed puberty.
Infertility.
Muscle weakness.

Ocular cystinosis only affects the corneas of the eyes, and typically, the only sign that is present is light sensitivity. No symptoms involving the kidneys will develop.

What Causes Cystinosis?
Cystinosis comes from CTNS gene abnormality, which makes instructions to produce the cystinosin protein. Cystinosin protein is supposed to help cystine be transported from the lysosome.
When cystinosin does not work:
Cystine builds up inside the cells.
Cystine makes crystals.
Crystals cause organ damage.

Cystinosis is passed from parents to a child through genes. Mostly, both parents carry one copy of the defective gene but do not show any symptoms themselves. When a child inherits the defective gene from both parents, the child develops cystinosis. This condition is lifelong because of the genetic defect present at birth.

Diagnosis and Tests:
How is cystinosis diagnosed?
The doctor will want to learn about your symptoms and medical history, and will do a physical exam. Tests will be done to help figure out your diagnosis.

What tests will be done to diagnose cystinosis?
These are some tests a healthcare provider will suggest to check for cystinosis:
Blood Test: A sample of your blood will be taken to measure the cystine levels in your white blood cells.
Genetic Testing: A geneticist will check for a mutation in the CTNS gene.
Urinalysis: A urine test will check for the loss of excess minerals, nutrients, electrolytes, and amino acids.
Eye Examination: Cystine crystals might be present in your corneas, and an eye doctor will check for them using a highly magnified slit lamp.

If you have a family history of cystinosis and are pregnant, you might be able to get prenatal tests (like amniocentesis) to see if your baby might have cystinosis. Your healthcare provider can test a sample of the amniotic fluid that contains cells from the developing baby to check for cystine.

Cystinosis can also be tested for using a different prenatal method known as chorionic villus sampling. This method analyzes the structures known as chorionic villi that are found in the placenta.

Treatment and Management:
Cysteamine:
Cystinosis patients receive cysteamine as their first-line treatment. It is a cystine-depleting treatment. This therapy works by lowering the cystine levels inside the cells. It helps prevent crystal accumulation and reduces ongoing organ damage. Nephropathic cystinosis is the most severe form of the disease.

When started early, cysteamine plays an important role in pediatric renal lysosomal disorder treatment. It can significantly slow the progression of kidney damage, delay the onset of kidney failure, and postpone the need for kidney transplantation. Used consistently from an early age, cysteamine has helped many children delay transplantation until adulthood, improve growth and support overall development.

Cystagon™ is an available oral formulation that contains cysteamine. In order for cystine reduction to be effective, patients taking Cystagon™ must take it every 6 hours. Procysbi™ is made for patients aged 6 years and older, and is a delayed-release formulation that allows for dosing every 12 hours which improves adherence to the treatment.

Oral cysteamine does not effectively treat eye involvement. For patients with ocular cystinosis, cystine can accumulate in the cornea, and forms a corneal cystine crystal that causes serious light sensitivity and discomfort in the eyes. To treat this, FDA approves the use of Cystamine eye drops Cystadrops™ which is used as part of cystinosis cystine crystal corneal therapy. This eye drop is used hourly while patients are awake. They help to dissolve corneal crystals, reduce photophobia, and improve overall eye comfort.

Supportive Treatments:
Children with cystinosis may need additional supportive treatments based on their specific symptoms. Fanconi syndrome treatment includes:
Drinking large amounts of fluids and electrolytes to avoid too much water loss.
Taking medications to keep the electrolyte levels
Taking medications to help the kidneys absorb phosphate.

Other treatments for cystinosis may include:
Therapy with growth hormone.
Insulin to treat diabetes that requires insulin injections.
Testosterone for patients with hypogonadism.
Therapy for speech and language
Genetic counseling.

Some children with feeding difficulties may need a feeding tube (gastronomy tube) to help them receive adequate nutrition and medications.
Treatment for ocular cystinosis may additionally include:
Light avoidance.
Sunglasses.
Eyedrops.
Very rarely, a corneal transplant may be necessary.

Kidney Transplantation in Cystinosis:
Transplantation is the best course of action for most Nephropathic and intermediate cystinosis patients, no matter how good the treatments. Fortunately for us:
Kidneys do not accumulate cystine
Transplant success rates are remarkably high

Even so, patients on cysteamine will need to stay on it to combat the cystine piling up in other organs.

Side Effects and Treatment Challenges:
Cysteamine causes many side effects such as:
Nausea
Vomiting
Gastrointestinal discomfort
Unpleasant odor in breath and sweat

Adverse effects can be lessened by doses and other medications, so these side effects won’t be as big of an issue.

Long-Term Outlook for People With Cystinosis:
Decades ago, cystinosis was often fatal in childhood. Today, new approaches in pediatric renal lysosomal disorder treatment, early diagnosis, and transplantation have dramatically improved survival.
Most people with cystinosis can now:
live into adulthood
have a good quality of life
obtain an education and a career
start a family

However, ongoing treatment and regular medical check ups are still very important.

Can Cystinosis Be Prevented?
Cystinosis is a genetic condition and can be managed. Families may benefit from genetic counseling and carrier screening to better understand their genetic risks.

A Note from Indian Pharma Network:
Cystinosis is a complex rare condition. It can be managed when diagnosed early and treated appropriately. Recent progresses in cystine depleting treatment, kidney care, and targeted therapies for corneal cystine crystal therapy have greatly improved the prognosis for patients across the world.

With the right medical attention, education, and support, people with cystinosis can live longer, healthier and more meaningful lives.

Disclaimer:
This content is informational and is not a substitute for professional medical care. Only a trained medical professional may make decisions on diagnosis and treatment.

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