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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
2001 Mar 22 [updated 2014 Jan 30].



Nephropathic cystinosis in untreated children is characterized by renal tubular Fanconi syndrome, poor growth, hypophosphatemic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine crystals in almost all cells, leading to cellular destruction and tissue dysfunction. The typical untreated child has short stature, light complexion, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these therapies, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized only by photophobia resulting from corneal cystine crystal accumulation.


The diagnosis of cystinosis is established by documenting: Renal tubular Fanconi syndrome: increased urinary losses of essential nutrients including electrolytes (sodium, potassium, bicarbonate), minerals (calcium, phosphate, magnesium), glucose, amino acids, carnitine, and water; Typical cystine crystals in the cornea on slit lamp examination; Increased cystine content of leukocytes. Identification of two pathogenic variants in CTNS, the only gene in which mutation is currently known to be cause cystinosis, is confirmatory.


Treatment of manifestations: Renal tubular Fanconi syndrome is treated by replacement of renal losses; phosphate and vitamin D supplements prevent and treat severe hypophosphatemic rickets; skeletal deformities or metabolic bone disease should be addressed early with the help of orthopedic specialists. Nutrition must be adequate to minimize failure to thrive in infants. Cysteamine hydrochloride eyedrops dissolve corneal crystals within months and relieve photophobia within weeks. Required hormone replacement therapies may include: L-thyroxine, insulin, growth hormone, and/or testosterone. Physical and speech therapy is helpful for the muscle deterioration and swallowing difficulties of older individuals. Prevention of primary manifestations: Therapy with cystine-depleting agents begun as soon as the diagnosis is made or (if possible) shortly after birth may attenuate the renal tubular Fanconi syndrome and significantly slow the progression of glomerular damage; however, renal damage present at the time of diagnosis is irreversible. With optimal symptomatic and cystine-depleting therapy affected individuals grow at a normal rate but generally do not recover lost height unless human growth hormone is administered. Prevention of secondary complications: Those who have undergone renal transplantation should be monitored for signs of immunodeficiency and infection; carnitine supplementation may improve muscle strength; treatment with proton pump inhibitors helps relieve cysteamine-induced gastric acid hypersecretion. Surveillance: Evaluation by a nephrologist every 3-6 months depending on the severity of renal impairment; ophthalmologic evaluation every 1-2 years; assessment of bone mineralization throughout the disease course; fasting blood glucose concentration and testosterone concentration every 2-3 years (in males, starting before puberty); routine monitoring for late-onset complications by a multidisciplinary medical team. Agents/circumstances to avoid: Dehydration; sun exposure if photophobia is present. Evaluation of relatives at risk: Biochemical and/or molecular genetic testing (if the mutation status of the proband is known) allows for early diagnosis and treatment.


Cystinosis is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if both pathogenic variants have been identified in the family. For pregnancies at increased risk for nephropathic cystinosis, prenatal diagnosis is also possible biochemically, based on elevated cystine concentration in both chorionic villi and amniocytes.

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