Nephropathic cystinosis. An underestimated problem in pediatric nephrology


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Abstract

Pathogenesis and clinical signs of cystinosis, as well as Russian experience of the diagnosis and treatment of this disease are reviewed
Cystinosis is a rare autosomal-recessive disease resulting from intra-lysosomal cystine accumulation. The kidney damage leads to Fanconi syndrome with a progressive decline in renal function. Cornea, endocrine glands, nervous system, bones and muscles are also affected. The article highlights pathogenesis, clinical symptoms and treatment approach in cystinosis. Russian experience of diagnostics and treatment of cystinosis is summarized

References

  1. Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002; 1347:111-121
  2. Scriver C, Beaudet A, Sly W, Valle D. The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill 2001; 5085-5101
  3. Anikster Y, Lucero C, Guo J, Huizing M, Shotelersuk V, Bernardini I, McDowell G, Iwata F, Kaiser-Kupfer MI, Jaffe R, Thoene J, Schneider JA, Gahl WA. Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res 2000; 47:17-23 Broyer M, Gubler M. Cystinosis, from Oxford Textbook of Clinical Nephrology, 3rd Edition, Oxford University Press, 2005; 2367- 2373
  4. Gahl WA, Kaiser-Kupfer MI. Complications of nephropathic cystinosis after renal failure. Pediatr Nephrol 1987; 1:260-268.
  5. Theodoropoulos DS, Krasnewich D, Kaiser-Kupfer MI, Gahl WA. Classic nephropathic cystinosis as an adult disease. JAMA 1993; 270:2200-2204.
  6. Gahl WA. Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr 2003; 162[Suppl 1]:S38-41.
  7. Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, Schlesselman JJ, Corden BJ, Schneider JA. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987; 316:971-977
  8. Gahl WA, Thoene JG, Schneider JA, O'Regan S, Kaiser-Kupfer MI, Kuwabara T. Cystinosis: progress in a prototypic disease. Ann Intern Med 1988; 109:557-569.
  9. Kimonis VE, Troendle J, Rose SR. et al. Effects of early cysteamine therapy on thyroid function and growth in nephropathic cystinosis. J Clin Endocrinol Metab 1995; 80:3257-3261
  10. Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, Gahl WA. Long-term follow-up of welltreated nephropathic cystinosis patients. J Pediatr 2004; 145:555-560
  11. Kleta R, Kaskel F, Dohil R, Goodyer P, Guay-Woodford LM, Harms E, Ingelfinger JR, Koch VH, Langman CB, Leonard MB, Mannon RB, Sarwal M, Schneider JA, Skovby F, Sonies BC, Thoene JG, Trauner DA, Gahl WA. NIH Office of Rare Diseases. First NIH/Office of Rare Diseases Conference on cystinosis: past, present, and future. Pediatr Nephrol 2005; 20:452-454
  12. Markello TC, Bernardini IM, Gahl WA. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med 1993; 328:1157-1162
  13. 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; 84:137-146.
  14. Thoene JG. Cysteamine treatment of nephropathic cystinosis. Prog Clin Biol Res 1983; 127:125-131
  15. Tsilou ET, Rubin BI, Reed G, Caruso RC, Iwata F, Balog J, Gahl WA, Kaiser-Kupfer MI. Nephropathic cystinosis: posterior segment manifestations and effects of cysteamine therapy. Ophthalmology 2006; 113:1002-1009
  16. McDowell GA, Town MM, van't Hoff W, Gahl WA. Clinical and molecular aspects of nephropathic cystinosis. J Mol Med 1998; 76:295-302
  17. Kalatzis V, Cherqui S, Antignac C, Gasnier B. Cystinosin, the protein defective in cystinosis, is a H+−driven lysosomal cystine transporter. EMBO J 2001; 20:5940-5949
  18. Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP, van't Hoff W, Antignac CA. Novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 1998; 18: 319- 324
  19. Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, Guo J, Thoene J, Gahl WA. CTNS mutations in an American-based population of cystinosis patients. Am J Hum Genet 1998; 63:1352-1362
  20. Kalatzis V, Antignac C. Cystinosis: from gene to disease. Nephrol Dial Transplant 2002; 17:1883-1886
  21. Kleta R, Anikster Y, Lucero C, Shotelersuk V, Huizing M, Bernardini I, Park M, Thoene J, Schneider J, Gahl WA. CTNS mutations in African American patients with cystinosis. Mol Genet Metab 2001; 74:332-337
  22. McGowan-Jordan J, Stoddard K, Podolsky L, Orrbine E, McLaine P, Town M, Goodyer P, MacKenzie A, Heick H. Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur J Hum Genet 1999; 7:671-678.
  23. Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, Guo J, Thoene J, Gahl WA. CTNS mutations in an American-based population of cystinosis patients. Am J Hum Genet 1998; 63:1352-1362
  24. Thoene J, Lemons R, Anikster Y, Mullet J, Paelicke K, Lucero C, Gahl W, Schneider J, Shu SG, Campbell HT. Mutations of CTNS causing intermediate cystinosis. Mol Genet Metab 1999; 67:283-289
  25. Gahl WA, Bashan N, Tietze F, Schulman JD. Lysosomal cystine counter-transport in heterozygotes for cystinosis. Am J Hum Genet 1984; 36:77-82
  26. Ray TL, Tobias JD. Perioperative care of the patient with nephropathic cystinosis. Paediatr Anaesth 2004; 14:878-885
  27. Attard M, Jean G, Forestier L, Cherqui S, van't Hoff W, Broyer M, Antignac C, Town M. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum Mol Genet 1999; 8:2507-2514
  28. Gahl WA, Tietze F. Lysosomal cystine transport in cystinosis variants and their parents. Pediatr Res 1987; 21:193-196
  29. Gahl WA. Cystinosis coming of age. Adv Pediatr 1986; 33:95-126
  30. Middleton R, Bradbury M, Webb N, O'Donoghue D, Van't Hoff W. Cystinosis. A clinicopathological conference. "From toddlers to twenties and beyond" Adult-Paediatric Nephrology Interface Meeting, Manchester 2001. Nephrol Dial Transplant 2003; 18:2492-2495
  31. Theodoropoulos DS, Shawker TH, Heinrichs C, Gahl WA. Medullary nephrocalcinosis in nephropathic cystinosis. Pediatr Nephrol 1995; 9:412-418
  32. Bernardini I, Rizzo WB, Dalakas M, Bernar J, Gahl WA. Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome. J Clin Invest 1985; 75:1124-1130
  33. Manz F, Gretz N. Progression of chronic renal failure in a historical group of patients with nephropathic cystinosis. European Collaborative Study on Cystinosis. Pediatr Nephrol 1994; 8:466-47
  34. Mahoney CP, Striker GE. Early development of the renal lesions in infantile cystinosis. Pediatr Nephrol 2000; 15:50-56
  35. Koizumi F, Koeda T, Wakaki K, Matumoto M, Kobashi K, Akao T, Fukase M. Cystinosis with marked atrophy of the kidneys and thyroid. Histological and ultrastructural studies in an autopsy case. Acta Pathol Jpn 1985; 35:145-155
  36. Busuttil DP, Liu Yin JA. The bone marrow in hereditary cystinosis. Br J Haematol 2000; 111:385
  37. Tsilou ET, Rubin BI, Reed GF, Iwata F, Gahl W, Kaiser-Kupfer MI. Age-related prevalence of anterior segment complications in patients with infantile nephropathic cystinosis. Cornea 2002; 21:173-176.
  38. Wong VG. Ocular manifestations in cystinosis. Birth Defects Orig Arctic Ser 1976; 12:181-186
  39. Broyer M, Gubler M. Cystinosis. In: Oxford Textbook of Clinical Nephrology, 3rd Edition, Oxford University Press, 2005; 2367- 2373
  40. Gahl WA. Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr 2003; 162[Suppl 1]:S38-S41

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