Nephropathic cystinosis in untreated children is characterized by renal tubular Fanconi syndrome, poor growth, hypophosphatemic rickets, impaired glomerular function, and accumulation of cystine crystals in almost all cells, leading to tissue destruction. The typical untreated child has short stature, light complexion, rickets, and photophobia. Growth failure is generally noticed between ages six and nine 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. Non-nephropathic cystinosis is characterized only by photophobia resulting from corneal cystine crystal accumulation.
The diagnosis of cystinosis is established by documenting: (1) 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; (2) typical cystine crystals in the cornea on slit lamp examination; and (3) increased cystine content of leukocytes. Identification of two mutations in CTNS, the only gene in which mutation is currently known to be cause cystinosis, is confirmatory.
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 when both disease-causing mutations have been identified in the family. For pregnancies at increased risk for nephropathic cystinosis, prenatal testing is also available biochemically, based on elevated cystine concentration in both chorionic villi and amniocytes.