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Cystinosis is a rare genetic metabolic disease that causes cystine, an amino acid, to accumulate in lysosomes of various organs of the body such as the kidneys, liver, eyes, muscles, pancreas, brain, and white blood cells. Although cystinosis primarily affects children, a form of the disease also occurs in adults.


In cystinosis, the cystine content of cells increases to an average of 50 to 100 times its normal value. This increase is caused by an abnormality in the transport of cystine out of a sac-like compartment of the cell called the lysosome. Because of cystine's low solubility in water, this amino acid forms crystals that accumulate within the lysosomes of cells. The accumulation of cystine is believed to destroy the cells.

There are three basic forms of cystinosis: infantile nephropathic cystinosis; late-onset nephropathic cystinosis; and benign non-nephropathic cystinosis.

Infantile nephropathic cystinosis

Children with infantile cystinosis usually appear normal at birth and during the first six to eight months of life. As Fanconi syndrome (a tubular dysfunction of the kidneys causing an impairment in the kidneys' ability to reabsorb minerals and nutrients back into the bloodstream) develops, sodium and water depletion occurs, leading to polyuria (excessive urination) and polydipsia (excessive thirst). Affected children become especially vulnerable to dehydration. This tubular abnormality, in addition to an abnormality in sweat production, often leads to recurrent fevers as a presenting symptom.

By one year of age, children generally exhibit growth retardation, rickets (inadequate deposition of minerals in developing cartilage and newly formed bone, causing abnormalities in shape and structure of bones), metabolic acidosis (excessive acid in the blood), and other chemical evidence or renal tubular abnormalities of the kidney, such as increased renal (kidney) excretion of glucose, amino acids, phosphate, and potassium. However, more subtle clinical and biochemical evidence of the disease can be detected at a much earlier age by careful examination of at-risk children (those with a sibling or other relative with the disease). As a child with infantile nephropathic cystinosis ages, failure to thrive is apparent.

Without therapeutic intervention, children remain below the norm in both height and weight throughout life. The typical patient with infantile nephropathic cystinosis has short stature, retinopathy (retinal disorder), photophobia (light sensitivity), and onset of Fanconi's syndrome in the first year of life. By one to two years of age, corneal cystine crystals and rickets are evident. Glomerular failure (the glomerulus is a small structure in the kidney made up of a cluster of capillaries) progresses, and end-stage renal disease occurs by about nine to ten years of age.

Late-onset cystinosis

In late-onset nephropathic cystinosis, the age of onset ranges from 2–26 years; however, the typical age at which this condition presents is 12–13 years. If more than one sibling develops late-onset cystinosis, their age of onset and symptoms are generally similar. Patients with this condition develop crystalline deposits in the cornea and conjunctiva (mucous membrane lining the eyelids) as well as in the bone marrow. Although patients with late-onset cystinosis often do not develop full-blown Fanconi's syndrome, renal failure progresses to such a degree that kidney transplantation is necessary, as in the case of infantile nephropathic cystinosis. These individuals are usually in end-stage renal failure within a few years of diagnosis.

Benign non-nephropathic cystinosis

Formerly known as adult cystinosis, benign nonnephropathic cystinosis is usually discovered by chance when an ophthalmologic (eye) examination reveals crystalline opacities within the cornea and conjunctiva. As in patients with infantile nephropathic cystinosis, those with benign cystinosis may also have photophobia; however, light sensitivity may not develop until middle age and is usually not as debilitating. Because the only patients diagnosed with benign cystinosis are those who undergo slit-lamp (a lamp constructed such that intense light is emitted through a slit) eye examination, it is possible that many individuals with this form of the disease never experience eye symptoms and are never diagnosed. Patients with benign cystinosis develop crystalline deposits in their bone marrow and white blood cells but do not develop renal dysfunction or retinopathy.

Genetic profile

Cystinosis is an autosomal recessive genetic disease. The term "autosomal" refers to a gene situated on one of the 22 of the 23 pairs of chromosomes other than a sex chromosome (or the X or Y chromosome). The term "recessive" refers to an allele, or a form of a gene that may be expressed and/or active; however, the "dominant" form of the gene on the other chromosome usually takes over enough of the gene's normal function to prevent symptoms of a disorder. Each parent of a child with cystinosis carries one abnormal (recessive) gene and one normal gene. Thus, the child must inherit an abnormal (or altered) gene from each parent to develop the disease. In addition, when a child develops cystinosis, the parents are almost always surprised because they never exhibited any symptoms of the disease. The recessive gene may lie dormant for generations until two people with the abnormal gene come together and have children.

Each time two such cystinosis carriers—persons with one copy of the altered gene and one copy of a normal or functioning gene—have a child together, there is a one-in-four chance (25% risk) of having a child with cystinosis; two-in-four (50% risk) the child will not have cystinosis but will be a carrier; and a one-in-four chance the child will not have cystinosis or be a carrier. Also, every unaffected sibling of a child with cystinosis has a two-in-three (67%) chance of being a carrier (having one copy of the abnormal gene and one copy of a normal gene), like his or her parents.

Scientists have mapped the cystinosis gene, CTNS, to the short arm of chromosome 17 (at location 17p13). Mutations (changes) in the cystinosis gene (specifically, a deletion of a particular part of the gene) have been found to cause all three types of cystinosis. However, this deletion is difficult to identify in some individuals for reasons that are uncertain. In these individuals, extensive and very sophisticated laboratory work (molecular genetic testing ) to identify and prove the existence of the deletion would be necessary.

In patients of Northern European descent, for example, there is about a 50/50 probability that an individual with cystinosis has the deletion. Genetic testing is under investigation for populations of these regions, but until details of the methodology are refined, measurement of lysosomal cystine in white cells and fibroblasts (any cell or corpuscle from which connective tissue is developed) will remain the state-of-the art and the most broadly based general method for diagnosing cystinosis.


It is estimated that 2,000 individuals worldwide have cystinosis, although exact figures are difficult to obtain because the disease often remains undiagnosed. In the United States, the disease is believed to affect approximately 400 individuals.

Signs and symptoms

Although the symptoms of cystinosis vary, depending on the type of disease present, general symptoms include:

  • acidosis
  • dehydration
  • rickets
  • growth retardation
  • renal glomerular failure
  • corneal ulcerations and retinal blindness
  • delayed puberty
  • swallowing difficulties


Cystinosis may be diagnosed prenatally by examining cystine levels in chorionic villi (obtained by chorionic villus sampling, usually done at 10–12 weeks gestation) or in cells contained in amniotic fluid (obtained by amniocentesis , usually done at 16–18 weeks gestation). In early infancy, cystinosis is usually diagnosed by measuring free cystine in white blood cells and skin fibroblasts.

Chorionic villus sampling

Chorionic villus sampling (tissue sample of tiny pieces of placental tissue obtained by inserting a thin needle or narrow tube into the uterus) is performed at 10–12 weeks of gestation. Intracellular cystine levels are measured. The values in a fetus with cystinosis are more than 10 times greater than normal.


Amniocentesis (sample of amniotic fluid obtained by inserting a thin needle into the uterus) can be performed at 16–18 weeks of gestation.

White blood cell testing

When diagnosed early, the progressive kidney failure, retarded growth, and vision problems can be prevented or delayed by proper management and medication. The metabolic abnormality in cystinosis is the failure of the cellular lysosomes to release cystine. As a result, the free cystine in the lysosomes accumulates to many times the normal value. The diagnosis of cystinosis is therefore based in part on the measurement of free cystine in the tissues that accumulate this amino acid. This measurement is most easily accomplished in white blood cells. Whole blood contains red cells, which are rich in glutathione, a compound that can react with cystine. To prevent this reaction, white cells are separated from red cells. The white cells are kept cold to slow down reactions, then broken open, and frozen. Freezing prevents the reaction of cystine with compounds such as glutathione and precipitates the cell protein. These steps stabilize the cystine content of the preparation.

Skin fibroblast testing

Cultured skin fibroblasts may also be used to diagnose cystinosis. Because of the increased time and costs, white blood cells are usually sent for testing first. Skin fibroblast testing (biopsy) is also more invasive than a blood sample. On rare occasions the expression of the abnormality in white cells is borderline for diagnosis. Thus, confirmation using fibroblasts is definitive.

Treatment and management

Cystinosis is treated by a variety of pharmacologic and nonpharmacologic therapies as well as by surgical transplantation.

Pharmacologic therapy

The aim of specific treatment for cystinosis is to reduce cystine accumulation within the cells. This goal is achieved by cysteamine treatment, which has proven effective in delaying or preventing renal failure. Cysteamine treatment also improves growth in children with cystinosis. The growth improvement with cysteamine bitartrate usually allows the patient to maintain growth along a percentile but does not usually aid in achieving "catch-up" growth.

The Food and Drug Administration (FDA) approved a capsule form of cysteamine bitartrate called Cystagon in August 1994. However, oral cysteamine does not prevent the progression of ocular lesions and has many potential side effects. Little is known about the drug's long-term effects. The main disadvantage of cysteamine treatment is the need for four daily capsules (every six hours) and the sulfurous breath it causes. Cysteamine treatment is also expensive.

Many children with cystinosis receive growth hormone, and some have had improvements in height. There is also evidence that indomethacin (Indocin) increases appetite, decreases urine volume, decreases water consumption, and improves growth in pretransplanted patients with cystinosis.

Vitamin/mineral supplementation

The symptomatic treatment of the Fanconi's syndrome is essential in patients with cystinosis. The urinary losses of water, salts, bicarbonate, and minerals must be replaced. Most children receive a solution of sodium and potassium citrate, as well as phosphate. Some also receive extra vitamin D.

Organ transplantation

Kidney transplantation has proven useful in patients with cystinosis. If a patient with cystinosis receives a kidney transplant and reaches adulthood, the new kidney will not be affected by the disease. However, without cysteamine treatment, kidney transplant recipients can develop complications in other organs due to the continued cystine accumulation in the body. These complications can include muscle wasting, difficulty swallowing, diabetes , hypothyroidism, and blindness. Not all older patients, however, develop these symptoms.

In both young children with cystinosis and older patients with a kidney transplant, cysteamine eye drops may be useful in removing the corneal cystine crystals and reduce photophobia. However, the drops have not yet received FDA approval.


Since 1980, the prognosis of a child with cystinosis has greatly improved. However, if children with the disease receive no treatment, they rarely survive past the age of nine or ten.



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Vester U., M. Schubert, G. Offneer, and J. Brodehl. "Distal myopathy in nephropathic cystinosis." Pediatric Nephrology 14 (January 2000): 36–38.


Cystinosis Foundation. 2516 Stockbridge Dr., Oakland, CA 94611. (800) 392-8458. <>.

Cystinosis Research Network. 8 Sylvester Rd., Burlington, MA 01803. (866) CURE NOW. Fax: (781) 229-6030. <>.

National Center for Biotechnology Information. National Library of Medicine, Building 38A, Room 8N805, Bethesda, MD 20894. (301) 496-2475. <>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <>.


Cystinosis Pediatric Database (PEDBASE). <>.

"What Is Cystinosis?" The Cystinosis Research Network. <>.

Genevieve T. Slomski, PhD