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Cystinosis Clinical Presentation

  • Author: Ewa Elenberg, MD, MEd; Chief Editor: Craig B Langman, MD  more...
Updated: Aug 30, 2015


Cystinosis is classified into 2 general phenotypes: nephropathic and nonnephropathic cystinosis (benign variant).

  • Nephropathic cystinosis is further subdivided into infantile and late-onset (intermediate cystinosis), based on the age at presentation.
    • Nephropathic infantile cystinosis is the most common and most severe variant.
      • Symptoms of multiorgan involvement may be mild to severe, depending on the patient's age at diagnosis, the age when treatment was instituted and genetic factors.
      • Early in the natural history of infantile nephropathic cystinosis, clinical involvement follows a fairly predictable chronology. Patients usually present during the first year of life with polyuria, polydipsia, dehydration, metabolic acidosis (normal anion gap hyperchloremic acidosis), hypophosphatemic rickets, failure to thrive, and laboratory findings consistent with Fanconi syndrome. If untreated, renal failure develops by age 7-10 years.
      • Oral cysteamine therapy postpones the need for renal transplantation.
      • Renal transplantation has prolonged the lives of children with cystinosis. Renal transplantation is highly successful, disease does not recur in the graft, but cystine continues to accumulate in other tissues, resulting in such complications as eye disease (eg, severe photophobia, corneal ulcerations, retinal blindness), delayed puberty, hypothyroidism, pancreatic disease (eg, exocrine insufficiency, insulin-dependent diabetes mellitus), liver disease (eg, hepatosplenomegaly, nodular degenerative hyperplasia), distal vacuolar myopathy, swallowing difficulties, and CNS involvement (eg, calcifications, atrophy, pseudotumor cerebri).
    • Late-onset (intermediate) nephropathic cystinosis is a more indolent form of the disease. The age at manifestation is later; most commonly in early adolescence. Symptoms are usually restricted to kidneys (eg, less severe form of Fanconi syndrome, proteinuria) and eyes (eg, photophobia). Progression of the disease is slower; end-stage renal disease (ESRD) occurs after age 15 years.
  • Nonnephropathic cystinosis is considered a benign variant and is usually diagnosed by an ophthalmologist treating patients for photophobia. Photophobia may not begin until middle age and is not usually as debilitating as in the nephropathic form of the disease. Slit-lamp examination reveals corneal crystal deposits. In addition to the eye, cystine crystals are present in the bone marrow and leukocytes but are absent in the kidney and the retina.


A typical cystinotic patient has pale blond hair and blue eyes, although the disease also occurs among dark-haired individuals with brown eyes.

  • Initial presentation of infantile nephropathic cystinosis
    • The initial symptoms include polydipsia, polyuria, vomiting, loss of appetite, constipation, and failure to thrive.
    • The first signs may go unrecognized for several months until the patient develops severe dehydration, electrolyte imbalance, and metabolic acidosis during a mild illness. Some children may have recurrent bouts of fever and manifestations of heat intolerance (becoming red like beets) caused by a defect in sweat production.
    • Patients typically have short stature and renal Fanconi syndrome.
    • They have poor appetite, crave salty and hot and spicy foods, and prefer specific food textures. Each patient has specific food preferences that may already be evident by age 2 years.
  • Initial presentation of late-onset nephropathic (intermediate) cystinosis
    • Most cases are diagnosed by age 12 years.
    • Complete Fanconi syndrome often does not develop in late-onset cystinosis, but renal function deteriorates as in infantile nephropathic cystinosis, and patients often experience end-stage renal failure within a few years of diagnosis.
  • Nephropathic cystinosis (progressive disease)
    • Children younger than 1 year usually show growth retardation, rickets, metabolic acidosis, and other chemical evidence of renal tubular abnormalities, such as increased renal excretion of glucose, amino acids, phosphate, and potassium. They may require frequent hospital admissions because of dehydration.
    • As children age, failure to thrive is prominent. Without specific therapy, children remain below the third percentile in both height and weight throughout life.
    • Corneal crystals are apparent by age 1-2 years. The untreated cornea is packed with crystals by age 3-4 years, leading to photophobia in early childhood.
    • By age 7-10 years, previously noted symptoms become more severe, and patients develop increased proteinuria, progressive renal failure, increased photophobia, and thyroid insufficiency.
    • ESRD develops in adolescence, usually at age 10-13 years. The good adherence to therapy slows down the progression of renal failure by several more years.
    • Sexual maturation is delayed.
    • Males have hypogonadism and are infertile.
    • Retinal damage does not occur until the second or third decade of life.
    • Cerebral calcifications and muscular and swallowing difficulties cluster around the third decade of life.
    • The major complication of cystinosis in patients older than 20 years is legal blindness, distal vacuolar myopathy, cerebral calcifications or atrophy, swallowing dysfunction, diabetes mellitus, and liver disease (eg, hepatomegaly, nodular degenerative hyperplasia).


See the list below:

  • All forms of cystinosis have autosomal recessive patterns of inheritance. Cystinosis is caused by a defect in transport of cystine across the lysosomal membrane due to defective function of the lysosomal membrane protein cystinosin, resulting from mutations of the cystinosis gene (CTNS). CTNS resides on chromosome 17p13. The CTNS gene has 12 exons, the last 10 of which code for cystinosin.
  • Cystinosin (an integral lysosomal membrane protein) has 367 amino acids and 7 transmembrane domains. In nephropathic cystinosis patients, CTNS mutations can cause either an absence of cystinosin or a disruption of transmembrane domains and loss of protein function, leading to inhibition of cystine transport through the lysosomal membrane (which is carrier-dependent). More than 80 different CTNS mutations (missense, nonsense, splice-site, deletion, and promoter mutations) are described in patients with nephropathic cystinosis; the most common are 57 kilobases (kb) (approximately 60% of the mutations in US patients).
  • Mutations of CTNS that affect functionally unimportant regions of cystinosin account for a milder clinical course. The various CTNS mutations can explain why patients have a wide spectrum of clinical symptomatology.
  • The parents of patients with cystinosis are obligate heterozygotes for cystinosis; they each carry a single gene for the disease. Individuals heterozygous for cystinosis have never been reported to have cystine crystals in any tissue or cell. Despite the clinically normal appearance of individuals who are heterozygous for cystinosis, their polymorphonuclear cells contain an increased amount of cystine.
  • Late-onset (intermediate) cystinosis appears to be due to the inheritance of a mutation known to cause infantile disease in one allele and a relatively less clinically severe mutation in the other or due to the inheritance of a relatively less severe mutation in both alleles.
Contributor Information and Disclosures

Ewa Elenberg, MD, MEd Associate Professor of Pediatrics, Renal Section, Texas Children's Hospital, Baylor College of Medicine

Ewa Elenberg, MD, MEd is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Adrian Spitzer, MD Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Raptor Pharmaceuticals; Eli Lilly and Company; Dicerna<br/>Received grant/research funds from NIH for none; Received grant/research funds from Raptor Pharmaceuticals, Inc for none; Received grant/research funds from Alexion Pharmaceuticals, Inc. for none; Received consulting fee from DiCerna Pharmaceutical Inc. for none.

Additional Contributors

Uri S Alon, MD Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children's Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine

Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research

Disclosure: Nothing to disclose.

  1. Nesterova G, Gahl W. Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2008 Jun. 23(6):863-78. [Medline].

  2. [Guideline] Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of chronic kidney disease. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2008. [Full Text].

  3. Procysbi (cysteamine bitartrate) [package insert]. Novato, California: Raptor Pharmaceuticals Inc. August 2015. Available at [Full Text].

  4. Chevalier RL, Forbes MS. Generation and evolution of atubular glomeruli in the progression of renal disorders. J Am Soc Nephrol. 2008 Feb. 19(2):197-206. [Medline].

  5. Besouw MT, Bowker R, Dutertre JP, et al. Cysteamine toxicity in patients with cystinosis. J Pediatr. 2011 Dec. 159(6):1004-11. [Medline].

  6. Van Stralen KJ, Emma F, Jager KJ, et al. Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol. 2011 Oct. 6(10):2485-91. [Medline].

  7. Andrews PA, Sacks SH, van't Hoff W. Successful pregnancy in cystinosis. JAMA. 1994 Nov 2. 272(17):1327-8. [Medline].

  8. Almond PS, Matas AJ, Nakhleh RE. Renal transplantation for infantile cystinosis: long-term follow-up. J Pediatr Surg. 1993 Feb. 28(2):232-8. [Medline].

  9. Baum M. The Fanconi syndrome of cystinosis: insights into the pathophysiology. Pediatr Nephrol. 1998 Aug. 12(6):492-7. [Medline].

  10. Bendavid C, Kleta R, Long R, et al. FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis. Hum Genet. 2004 Nov. 115(6):510-4. [Medline].

  11. Cystaran (cysteamine ophthalmic solution) [package insert]. Gaithersburg, MD: Sigma-tau Pharmaceuticals, Inc. October, 2012. Available at [Full Text].

  12. Dohil R, Newbury RO, Sellers ZM, et al. The evaluation and treatment of gastrointestinal disease in children with cystinosis receiving cysteamine. J Pediatr. 2003 Aug. 143(2):224-30. [Medline].

  13. Elenberg E, Norling LL, Kleinman RE, Ingelfinger JR. Feeding problems in cystinosis. Pediatr Nephrol. 1998 Jun. 12(5):365-70. [Medline].

  14. Facts and Comparisons. Cysteamine bitartrate. Drug Facts and Comparisons. 5th ed. St. Louis, MO: Facts and Comparisons; 2000. 590-1.

  15. Foreman JW. Metabolic disorders. Pediatric Nephrology. Baltimore, MD: Lippincott Williams & Wilkins; 1994. 537- 57.

  16. Gahl WA. Cystinosis coming of age. Adv Pediatr. 1986. 33:95-126. [Medline].

  17. Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med. 2007 Aug 21. 147(4):242-50. [Medline]. [Full Text].

  18. Gahl WA, Reed GF, Thoene JG. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med. 1987 Apr 16. 316(16):971-7. [Medline].

  19. Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002 Jul 11. 347(2):111-21. [Medline].

  20. Jonas AJ, Schulman JD, Matalon R, et al. Cystinosis in non-caucasian children. Johns Hopkins Med J. 1982 Sep. 151(3):117-21. [Medline].

  21. Kleta R, Kaskel F, Dohil R, et al. First NIH/Office of Rare Diseases Conference on Cystinosis: past, present, and future. Pediatr Nephrol. 2005 Apr. 20(4):452-4. [Medline].

  22. Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan. 21(1):110-3. [Medline].

  23. Markello TC, Bernardini IM, Gahl WA. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med. 1993 Apr 22. 328(16):1157-62. [Medline].

  24. Saleem MA, Milford DV, Alton H, et al. Hypercalciuria and ultrasound abnormalities in children with cystinosis. Pediatr Nephrol. 1995 Feb. 9(1):45-7. [Medline].

  25. Schneider JA, Katz B, Melles RB. Update on nephropathic cystinosis. Pediatr Nephrol. 1990 Nov. 4(6):645-53. [Medline].

  26. Smolin LA, Clark KF, Schneider JA. An improved method for heterozygote detection of cystinosis, using polymorphonuclear leukocytes. Am J Hum Genet. 1987 Aug. 41(2):266-75. [Medline]. [Full Text].

  27. Sonies BC, Almajid P, Kleta R, Bernardini I, Gahl WA. Swallowing dysfunction in 101 patients with nephropathic cystinosis: benefit of long-term cysteamine therapy. Medicine (Baltimore). 2005 May. 84(3):137-46. [Medline].

  28. Swinford RD, Elenberg E, Ingelfinger JR. Persistent renal disease. Nutritrition in Pediatrics: Basic Science and Clinical Applications. Hamilton, Ontario: BC Decker; 1996. 493-515.

  29. The Cystinosis Collaborative Research Group. Linkage of the gene for cystinosis to markers on the short arm of chromosome 17. Nat Genet. 1995 Jun. 10(2):246-8. [Medline].

  30. Theodoropoulos DS, Krasnewich D, Kaiser-Kupfer MI, Gahl WA. Classic nephropathic cystinosis as an adult disease. JAMA. 1993 Nov 10. 270(18):2200-4. [Medline].

  31. Wuhl E, Haffner D, Gretz N, et al. Treatment with recombinant human growth hormone in short children with nephropathic cystinosis: no evidence for increased deterioration rate of renal function. The European Study Group on Growth Hormone Treatment in Short Children with Nephropathic Cy. Pediatr Res. 1998 Apr. 43(4 Pt 1):484-8. [Medline].

  32. Wuhl E, Haffner D, Offner G, et al. Long-term treatment with growth hormone in short children with nephropathic cystinosis. J Pediatr. 2001 Jun. 138(6):880-7. [Medline].

An 8-month-old male infant at the time his cystinosis is diagnosed.
The same child as in the previous image, at age 20 months, fed via gastric tube.
The same child as in the previous images, at age 3 years, fed via jejunal tube.
The same child as in the previous images, at age 4 years, on total parenteral nutrition via central line.
The same child as in the previous images, at age 9 years, off total parenteral nutrition for 1 year and tolerating oral intake.
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