• Elena Levtchenko
  • Francesco EmmaEmail author


Infantile nephropathic cystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene that encodes for cystinosin, a lysosomal cystine carrier. With time, cystine accumulation leads to cell dysfunction in various tissues; the kidneys are initially more involved. Most patients are asymptomatic at birth but present in the first or second year of life with failure to thrive, polyuria, dehydration, and/or rickets, which are secondary to the renal Fanconi syndrome. With very few exceptions, all patients have corneal cystine crystals by 18 months of age that can help in recognising the disease. The diagnosis of cystinosis is based on the demonstration of increased intra‐leucocyte cystine levels and of mutations in the CTNS gene (detection rate >95 %). In Northern Europe, 75 % of mutated alleles carry a 57‐kb deletion; all other types of mutations, generally resulting in a complete or severe loss of function of the cystinosin protein, have been described.

In the past decades, the introduction of cysteamine treatment and improvements in dialysis techniques and renal transplantation have considerably improved the prognosis of cystinosis. Cysteamine significantly delays progression to end‐stage renal failure, but cannot prevent it in most cases. The majority of patients live into adulthood, but, when not appropriately treated with cysteamine, develop other symptoms related to cystine accumulation in various tissues. These include retinal degeneration, hypothyroidism, diabetes mellitus, exocrine pancreatic insufficiency, pubertal retardation and gonadal dysfunction, restrictive pulmonary disease, myopathy, neurological deterioration, and liver involvement. Two milder forms of the disease (juvenile cystinosis and ocular cystinosis), caused by hypomorphic mutations of the CTNS gene, have also been reported; these patients present with milder symptoms later in childhood or with isolated corneal cystine depositions during adulthood.


Transient Receptor Potential Channel Vanilloid Exocrine Pancreatic Insufficiency Cystine Level Renal Fanconi Syndrome Restrictive Pulmonary Disease 
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  1. Attard M, Jean G, Forestier L et al (1999) Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum Mol Genet 8:2507–2514PubMedCrossRefGoogle Scholar
  2. Cherqui S, Kalatzis V, Trugnan G et al (2001) The targeting of cystinosin to the lysosomal membrane requires a tyrosine‐based signal and a novel sorting motif. J Biol Chem 276:13314–13321PubMedCrossRefGoogle Scholar
  3. Dohil R, Gangoiti JA, Cabrera BL et al (2010) Long-term treatment of cystinosis in children with twice-daily cysteamine. J Pediatr 156:823–827PubMedCrossRefGoogle Scholar
  4. Gahl WA (2003) Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr 162:S38–S41PubMedCrossRefGoogle Scholar
  5. Gahl WA, Thoene JG, Schneider JA (2002) Cystinosis. N Engl J Med 347:111–121PubMedCrossRefGoogle Scholar
  6. Gahl WA, Balog JZ, Kleta R (2007) Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med 147:242–250PubMedCrossRefGoogle Scholar
  7. Greco M, Brugnara M, Zaffanello M et al (2010) Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr Nephrol 25:2459–2467PubMedCrossRefGoogle Scholar
  8. Jézégou A, Llinares E, Anne C et al (2012) Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy. Proc Natl Acad Sci U S A 109: E3434–43PubMedCentralPubMedCrossRefGoogle Scholar
  9. Kalatzis V, Cherqui S, Antignac C et al (2001) Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. EMBO J 20:5940–5949PubMedCentralPubMedCrossRefGoogle Scholar
  10. Kleta R, Bernardini I, Ueda M et al (2004) Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr 145:555–560PubMedCrossRefGoogle Scholar
  11. Langman CB, Greenbaum LA, Sarwal M et al (2012) A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety. Clin J Am Soc Nephrol 7:1112–1120PubMedCentralPubMedCrossRefGoogle Scholar
  12. Levtchenko E, Blom H, Wilmer M et al (2003) ACE inhibitor enalapril diminishes albuminuria in patients with cystinosis. Clin Nephrol 60:386–389PubMedCrossRefGoogle Scholar
  13. Levtchenko E, de Graaf-Hess A, Wilmer M et al (2004) Comparison of cystine determination in mixed leukocytes vs polymorphonuclear leukocytes for diagnosis of cystinosis and monitoring of cysteamine therapy. Clin Chem 50:1686–1688Google Scholar
  14. Levtchenko EN, van Dael CM, de Graaf-Hess AC et al (2005) Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol 21:110–113Google Scholar
  15. Markello TC, Bernardini IM, Gahl WA (1993) Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med 328:1157–1162PubMedCrossRefGoogle Scholar
  16. Taranta A, Petrini S, Palma A et al (2008) Identification and sub-cellular localization of a new cystinosin isoform. Am J Physiol Renal Physiol 294:F1101–F1108PubMedCrossRefGoogle Scholar
  17. Taranta A, Wilmer MJ, van den Heuvel LP et al (2010) Analysis of CTNS gene transcripts in nephropathic cystinosis. Pediatr Nephrol 25(7):1263–1267PubMedCentralPubMedCrossRefGoogle Scholar
  18. Town M, Jean G, Cherqui S et al (1998) A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 18:319–324PubMedCrossRefGoogle Scholar
  19. Tsilou ET, Rubin BI, Reed GF et al (2002) Age-related prevalence of anterior segment complications in patients with infantile nephropathic cystinosis. Cornea 21:173–176PubMedCrossRefGoogle Scholar
  20. Van Stralen KJ, Emma F, Jager KJ et al (2011) Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol 6:2485–2491PubMedCentralPubMedCrossRefGoogle Scholar
  21. Wilmer MJ, Emma F, Levtchenko EN (2010) The pathogenesis of cystinosis: mechanisms beyond cystine accumulation. Am J Physiol Renal Physiol 299:F905–F916PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Pediatric NephrologyUniversity Hospitals Leuven, Catholic University LeuvenLeuvenBelgium
  2. 2.Division of Nephrology and DialysisOspedale Pediatrico Bambino Gesù, IRCCSRomeItaly

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