Cystinosis is a rare genetic disease in which the amino acid cystine builds up inside cells, gradually damaging the kidneys, eyes, muscles, and other organs. It affects roughly 1 in 100,000 to 200,000 newborns, and without treatment, the most severe form leads to complete kidney failure by age 10. With modern therapies, many people with cystinosis now live well into adulthood, with some surviving beyond age 50.
What Happens Inside the Cells
Every cell in your body contains tiny recycling compartments called lysosomes. These compartments break down proteins and other materials, then shuttle the leftover building blocks back out into the cell for reuse. One of those building blocks is cystine, a small molecule made from two linked amino acid units. Normally, a transport protein called cystinosin moves cystine out of the lysosome.
In cystinosis, mutations in the CTNS gene prevent cystinosin from working. More than 80 different mutations have been identified. The most common one, responsible for about 50 percent of cases in people of European descent, is a large deletion that wipes out the gene entirely. Other mutations produce a shortened, nonfunctional version of the protein. Either way, the result is the same: cystine gets trapped inside lysosomes, crystallizes, and slowly poisons the cell from the inside out.
Cystinosis follows an autosomal recessive inheritance pattern, meaning a child must inherit a defective copy of the CTNS gene from each parent. Parents who carry one working copy and one faulty copy typically have no symptoms themselves.
Three Types of Cystinosis
Cystinosis comes in three forms that differ by when symptoms appear and how quickly they progress.
Infantile nephropathic cystinosis is the most common and most severe, accounting for about 95 percent of all cases. Symptoms typically appear within the first year of life, beginning with kidney damage known as Fanconi syndrome (described below). Without treatment, affected children reach complete kidney failure by age 10.
Juvenile nephropathic cystinosis develops more slowly. Symptoms are often milder and less specific. Many patients aren’t diagnosed until their second decade of life, when light sensitivity drives an eye exam that reveals cystine crystals in the cornea. Untreated, kidney failure occurs between the mid-teens and mid-twenties.
Non-nephropathic (ocular) cystinosis is the mildest form. Cystine crystals accumulate in the cornea but the kidneys are largely spared. It is sometimes called the adult form because it may not be recognized until later in life.
How It Affects the Kidneys
The earliest and most prominent sign of infantile cystinosis is Fanconi syndrome, a condition in which the kidney’s filtering tubes lose the ability to reclaim essential substances. Normally, after the kidneys filter blood, they reabsorb most of the useful molecules before urine leaves the body. In Fanconi syndrome, that reabsorption fails. Glucose, amino acids, phosphate, potassium, sodium, bicarbonate, and magnesium all spill into the urine in excessive amounts.
The practical consequences are significant, especially for a growing infant. Children urinate far more than normal and become chronically dehydrated. The loss of phosphate weakens bones. The loss of bicarbonate makes the blood too acidic. Growth slows dramatically, and without intervention, children fall well below expected height and weight milestones. Even with treatment, many children eventually develop kidney failure during later childhood or adolescence and require a transplant.
Eye and Corneal Damage
Cystine crystals accumulate in the cornea early. In a natural history study, infants under one year had absent or minimal crystals, but every patient had visible crystals by 16 months of age. The crystal density increased steadily with age and plateaued by early adolescence.
These crystals cause increasing sensitivity to light (photophobia), which can become severe enough to make going outdoors painful. Over time, the crystals can also erode the surface of the cornea, causing recurrent eye injuries and scarring. Cysteamine eye drops can dissolve the crystals, but they require consistent, long-term use.
Complications Beyond the Kidneys and Eyes
Because cystine accumulates throughout the body, cystinosis is a systemic disease. The list of organs it can affect grows with age, particularly as patients survive longer thanks to better treatments.
The thyroid is commonly affected. Primary hypothyroidism, where the thyroid gland itself fails, is one of the more frequent complications and typically appears by the second decade of life. The endocrine pancreas can also be damaged, leading to diabetes. Gonadal failure, particularly in males, is another recognized complication.
Neurological and muscular problems emerge over time as well. Progressive muscle wasting, especially in the hands and lower legs, can develop and eventually interfere with walking and swallowing. These complications tend to appear in the second and third decades of life, underscoring why ongoing monitoring matters even after a kidney transplant.
How Cystinosis Is Diagnosed
The standard diagnostic test measures cystine levels inside white blood cells. A cystine level above 3.00 nmol half-cystine per milligram of protein in a specific type of white blood cell (polymorphonuclear leukocytes) confirms nephropathic cystinosis. Carriers of a single gene mutation typically fall below 1.00 on the same scale.
Genetic testing of the CTNS gene can confirm the diagnosis and identify the specific mutation. A slit-lamp eye exam can also reveal corneal crystals, which is often how the juvenile form is first detected. In practice, many infants are diagnosed after unexplained Fanconi syndrome prompts further investigation.
Treatment With Cysteamine
The primary treatment for cystinosis is a medication called cysteamine. It works by entering lysosomes and chemically reacting with the trapped cystine, converting it into a different compound that can escape through an alternative exit channel. This effectively bypasses the broken cystinosin transporter.
Cysteamine does not cure cystinosis, but starting it early and taking it consistently slows organ damage significantly. Children under 12 receive a dose calculated by body size, while older patients or those over 50 kilograms typically take up to 2 grams per day. The oral form is taken four times every 24 hours, which makes adherence genuinely challenging, especially for teenagers and young adults managing a lifelong medication schedule.
In addition to oral cysteamine, cysteamine eye drops are used to dissolve corneal crystals. Patients also typically need supplemental electrolytes and vitamins to replace what the kidneys fail to reabsorb, along with thyroid hormone replacement and other targeted treatments as complications arise.
Kidney Transplantation
When the kidneys fail, transplantation is the treatment of choice. The outcomes are encouraging: the transplanted kidney functions normally because it carries working copies of the CTNS gene, so cystine does not re-accumulate in the new organ’s filtering tubes. Fanconi syndrome does not recur.
There is a nuance, though. The recipient’s own immune cells, which still carry the genetic defect, can infiltrate the transplanted kidney and deposit cystine crystals in the surrounding tissue. Studies have found these crystals in biopsy samples, but they generally don’t cause clinical problems in the transplanted organ itself.
The more important limitation is that a kidney transplant does nothing to stop cystine from building up in the rest of the body. Patients still need cysteamine after transplantation to protect the thyroid, muscles, brain, and other organs. Complications like diabetes, hypothyroidism, and neurological involvement continue to develop during follow-up if systemic treatment lapses.
Gene Therapy on the Horizon
A phase 1/2 clinical trial at the University of California San Diego is testing a gene therapy approach. The treatment involves collecting a patient’s own blood stem cells, inserting a working copy of the CTNS gene using a modified virus, and infusing the corrected cells back into the patient. Six adults between ages 20 and 46 received the therapy between 2019 and 2022. With a median follow-up of 36 months and the longest follow-up reaching five years, the therapy has shown an acceptable safety profile and reduced cystine levels in white blood cells. It remains investigational, but represents the first attempt to address the root genetic defect rather than managing its downstream effects.