Please Remove Adblock
Adverts are the main source of Revenue for DoveMed. Please remove adblock to help us create the best medical content found on the Internet.


Last updated March 23, 2018

Approved by: Krish Tangella MD, MBA, FCAP


Intermediate magnification micrograph of Kidney with the changes of cystinosis. H&E stain.

What are the other Names for this Condition? (Also known as/Symptoms)

  • Intermediate Cystinosis
  • Nephropathic Cystinosis
  • Ocular Cystinosis

What is Cystinosis? (Definition/Background Information)

  • Cystinosis is a rare genetic disorder that is caused by mutations in the CTNS gene. This gene codes for the protein cystinosin, which is responsible for mobilizing the amino acid cystine from lysosomes. Lysosomes are the cellular waste-disposal and recycling organelles
  • When the protein is dysfunctional, cystine accumulates in the lysosomes. The symptoms of Cystinosis results from the accumulation of cystine crystals in cells of different tissues and organs
  • Cystinosis affects multiple body systems and organs. The signs and symptoms can include progressive kidney damage (Fanconi syndrome in infants), nutritional deficiencies of amino acids and essential minerals (lost through urine), growth retardation, enlarged liver and spleen, delayed puberty, lack of secondary sexual growth, and infertility
  • There are 3 types of Cystinosis:
    • Nephropathic Cystinosis: It is the most severe form with an onset during infancy
    • Intermediate Cystinosis: Although the symptoms are similar to the nephropathic type, the progression is much slower. The age of onset typically ranges from 8 years to adolescence
    • Non-Nephropathic or Ocular Cystinosis: It is considered a “benign” form of Cystinosis. The age of onset, though variable, is generally during mid-adulthood
  • A family history of Cystinosis is a major risk factor for children being born with Cystinosis. The condition is inherited in an autosomal recessive pattern, in which an individual must have two defective copies of the causative gene for manifestation of the condition
  • A diagnosis of Cystinosis can be made prenatally, if there is a known family history of the condition. After birth, a diagnosis of Cystinosis may require physical examination, symptom assessment, evaluation of family history, urine and blood tests, and other tests and examinations as needed
  • Some potential complications of Cystinosis include kidney failure and hypothyroidism in both infants and young children. There can be accumulation of cystine in the muscles and organs, such as the liver and pancreas, if the condition is left untreated. This can lead to gastrointestinal tract malfunction, high blood pressure, and memory loss (in the form of dementia)
  • The treatment options for Cystinosis include medication and surgery. Cysteamine is an oral medication, which depletes cystine from the cells; it has been found to be effective in slowing the progression of the condition. In case of end-stage renal failure, a kidney transplantation may be recommended
  • Since Cystinosis is a genetic condition, there are currently no methods or guidelines available for prevention of the condition. Expecting parents with a family history of the condition may benefit from genetic counseling
  • The prognosis of Cystinosis is reported to have improved in the past several decades. Earlier, the disorder was generally fatal; however, through medical advancements, the affected individuals are able to lead better lives, with an increased life expectancy (up to 50 years)

Who gets Cystinosis? (Age and Sex Distribution)

  • Cystinosis is reported to occur in 1 in every 100,000-200,000 individuals globally. The exception is people belonging to the region of Brittany, France, where the incidence rate is about 1 in 26,000
  • The age of onset of Cystinosis can be during infancy, adolescence, or adulthood
  • The disorder is seen to affect both genders; however, there is a marginal elevation in occurrence rate for males compared to females (1.4:1)
  • Cystinosis is a genetic disorder that is known to occur worldwide in individuals of all races and ethnicities

What are the Risk Factors for Cystinosis? (Predisposing Factors)

  • Cystinosis is a genetic disorder, and a family history of the disorder is a major risk factor for an individual to develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cystinosis? (Etiology)

  • Cystinosis is caused by mutation(s) in the CTNS gene
    • The gene codes for a protein called cystinosin. This protein is involved in the mobilization of cystine (an oxidized, dimeric form of the amino acid cysteine) from the lysosomes
    • Lysosome is an organelle within the cell that is responsible for degradation and management of cellular waste
    • When the gene is mutated, cystinosin becomes dysfunctional leading to cystine buildup within the lysosomes
    • The signs and symptoms of Cystinosis can be attributed to the accumulation of cystine crystals in various tissues and organs
  • This disorder is inherited in an autosomal recessive manner. This means that an individual must have 2 defective copies of the CTNS gene for the condition to manifest itself

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Cystinosis?

Cystinosis is classified into the following types based on the age of onset. The signs and symptoms of Cystinosis depend on the subtype of the disorder.

  • Nephropathic Cystinosis: The age of onset is infancy and the progression of the disorder is rapid
  • Intermediate Cystinosis: The age of onset is typically when the child is 8 years of age. The progression of the disorder is slower than compared to the nephropathic type of Cystinosis. This type is also known as Nephropathic Juvenile Cystinosis or Adolescent Cystinosis
  • Non-Nephropathic or Ocular Cystinosis: The age of onset is variable, but is typically observed during middle age. This condition is also known as “benign” Cystinosis

Signs and symptoms of Nephropathic Cystinosis:

  • Growth failure, noticeable by age 1
  • Kidney dysfunction known as renal Fanconi syndrome, wherein important minerals and nutrients (glucose, amino acids, calcium, magnesium, and phosphorus) are not reabsorbed, but excreted in urine
  • Polyuria, or increased production of dilute urine
  • Nutritional deficiencies, electrolyte imbalance
  • Feeding difficulties, poor appetite
  • Vomiting, dehydration
  • Reduced secretion of sweat, saliva, and tears
  • Collapse due to heat exhaustion, increased thirst
  • Acidic blood: The pH of blood is lower than normal which can cause abnormalities in body function
  • Fever, headaches
  • Hypophosphatemic rickets (a disorder of very low levels of phosphate in blood)
  • Bone abnormalities, muscle spasms
  • Abnormal gait, difficulty walking
  • Seizures
  • Abnormalities in several body parts, such as muscles, eyes, intestine, liver, brain, genitals and other parts
  • Sensitivity to light
  • Learning difficulties
  • Difficulty with visual understanding of distance between objects (called reduced visuospatial skills such as depth perception)
  • Difficulty identifying objects by touch
  • Psychological and social problems

Signs and symptoms of Intermediate Cystinosis (in addition to those listed under Nephropathic Cystinosis):

  • Reduced secretion of testosterone
  • Delayed puberty
  • Blindness
  • Muscle abnormalities, leading to difficulty in swallowing and breathing

Signs and symptoms of Ocular Cystinosis:

  • Sensitivity to light (photophobia)
  • Additionally, some of the signs and symptoms of both the nephropathic and intermediate form of Cystinosis may be seen

How is Cystinosis Diagnosed?

An accurate diagnosis of Cystinosis may be made through the following tests and procedures:

  • A physical examination with an assessment of the signs and symptoms
  • An evaluation of family history
  • Urine tests to check for loss of nutrients (as observed in Fanconi syndrome)
  • Blood tests: Cystine crystals in leukocytes can indicate Cystinosis; the abnormal crystals are seen in neutrophyls (polymorphonuclear leukocytes)
  • Eye exam with a slit lamp under high magnification to check for cystine crystals in the cornea
  • Genetic testing for confirmation: Prenatal testing of fetal cells to check for mutation(s) in CTNS gene, if there exists a family history of the condition

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cystinosis?

The potential complications of Cystinosis in infants and children include:

  • Kidney failure and end-stage kidney disease can take place in nephropathic and intermediate types, if the condition is not treated properly
  • Short stature
  • Hypothyroidism (with symptoms such as dry skin, feeling cold, constipation, and depression)
  • Increased secretion of stomach acids due to long-term treatment of the condition
  • Non-compliance of children with therapy, owing to foul-smelling medication and its side effects

Adults, who have had Cystinosis for several years, starting from childhood or adolescence may have the following complications:

  • Severe muscle wasting, due to lack of or inadequate treatment over a prolonged period, which can lead to difficulties in swallowing and breathing
  • Continued accumulation of cystine crystals in internal organs leading to enlarged liver and spleen, gastrointestinal issues (including ulcers, reflux disease, and esophageal inflammation), inflammatory bowel disease, and perforation of the intestine
  • High blood pressure
  • Atherosclerosis
  • Diabetes, owing to reduced digestive enzyme secretion by the pancreas
  • Pain in the eye due to spasm of eye muscles
  • Reduced night and/or color vision, loss of visual acuity
  • Reduced brain function in some adults, which may lead to dementia
  • Hearing loss
  • Kidney stones
  • Infertility in men
  • Non-compliance with therapy owing to foul-smelling medication and its side effects such as nausea and other gastrointestinal issues

How is Cystinosis Treated?

Cystinosis is a disorder that has no cure. The treatments are generally tailored toward addressing the signs and symptoms the affected individual experiences. A concerted effort by a team of specialists is often required to provide the best possible care for the affected individual, particularly if the affected individual is a child.

Cysteamine therapy is the mainstay of Cystinosis treatment:

  • Cysteamine works to lower cystine levels within the cells. It is known to slow progression of the condition and delay kidney failure
  • Cysteamine is an oral medication that is administered soon after diagnosis of the condition
  • It is recommended that this medication be taken life-long, since it is reported to help delay organ and system dysfunction
  • It is reported that cysteamine does not reach the cystine crystals in the cornea (eyes) effectively. For individuals with cystine accumulation in the eyes, an eye drop may be used
  • Cysteamine therapy can cause side effects, and so medications, such as proton pump inhibitors to reduce excess stomach acids and resultant nausea, may be prescribed

Symptomatic treatment: The individual symptoms are treated to provide relief to the affected individual.

  • Fanconi syndrome: Replacing fluids and electrolytes using anti-inflammatory medications to reduce urinary losses, acetylcholinesterase (AChe) inhibitors to slow progression of the condition, and mineral and vitamin supplementation
  • Gastronomy tube (Gtube) to help infants with feeding issues; for introduction of food and medicine
  • Nutrition and growth hormone therapy to help children grow better
  • Prescription medicine to treat hypothyroidism
  • If the diabetes is insulin-dependent, then insulin may be prescribed to help keep blood sugar levels under control
  • Males with low testosterone levels may be treated with testosterone to allow secondary sexual traits to develop
  • For sensitivity to light, avoiding bright lights and use of prescription eye drops (per a healthcare provider’s advice) may be helpful
  • Corneal transplantation may be recommended in individuals who experience pain in their eyes with corneal erosions
  • Kidney transplantation for end-stage kidney disease, if necessary
  • Special education, if needed

How can Cystinosis be Prevented?

Currently, there are no specific methods or guidelines to prevent Cystinosis, since it is a genetic condition.

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Cystinosis
  • Since the disorder is rare, keeping the parents and affected individuals informed with the latest scientific developments on the disorder may help them follow the progress and monitor the condition of their children better
  • Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended

What is the Prognosis of Cystinosis? (Outcomes/Resolutions)

  • The prognosis of Cystinosis has seen an improvement over the last several years, due to rapid scientific and medical advancements
  • Earlier, the life expectancy for individuals with nephropathic and intermediate forms of the disorder used to be 10 years. However, presently, medical advancements have helped extend the life expectancy well into adulthood. Many individuals are reported to survive into their 40s and even 50s, having better quality of lives
  • Cysteamine therapy has been helpful in delaying the progression of renal failure, and consequently of kidney transplantation, by several years
  • The procedure of kidney transplantation in itself has seen tremendous improvements, with 5-year survival rate at 100% for children with Nephropathic Cystinosis, since the year 2000 (according to certain studies). Nevertheless, about 5% of all childhood kidney failures are attributed to Cystinosis

Additional and Relevant Useful Information for Cystinosis:

  • Kidney transplantation is a procedure to surgically remove a damaged or diseased kidney and replace it with a healthy kidney, from a compatible donor.

The following article link will help you understand kidney transplantation:


What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: July 26, 2016
Last updated: March 23, 2018