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01-06-2008 | Review

Nephropathic cystinosis: late complications of a multisystemic disease

Authors: Galina Nesterova, William Gahl

Published in: Pediatric Nephrology | Issue 6/2008

Abstract

Cystinosis is a rare autosomal recessive disorder due to impaired transport of cystine out of cellular lysosomes. Its estimated incidence is 1 in 100,000 live births. End-stage renal disease (ESRD) is the most prominent feature of cystinosis and, along with dehydration and electrolyte imbalance due to renal tubular Fanconi syndrome, has accounted for the bulk of deaths from this disorder. Prior to renal transplantation and cystine-depleting therapy with cysteamine for children with nephropathic cystinosis, their lifespan was approximately 10 years. Now, cystinotic patients have survived through their fifth decade, but the unremitting accumulation of cystine has created significant non-renal morbidity and mortality. In this article we review the classic presentation of nephropathic cystinosis and the natural history, diagnosis, and treatment of the disorder’s systemic involvement. We also emphasize the role of oral cysteamine therapy in preventing the late complications of cystinosis.

Scriver C, Beaudet A, Sly W, Valle D Childs B, (2001) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, pp 5085–5101

Gahl WA, Thoene JG, Schneider JA (2002) Cystinosis. N Engl J Med 1347:111–121

Gahl WA (1986) Cystinosis coming of age. Adv Pediatr 33:95–126PubMed

Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser-Kupfer MI (2000) Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol Genet Metab 71:100–120PubMed

Manz F, Gretz N (1994) Progression of chronic renal failure in a historical group of patients with nephropathic cystinosis. European Collaborative Study on Cystinosis. Pediatr Nephrol 8:466–471PubMed

Gahl WA, Kaiser-Kupfer MI (1987) Complications of nephropathic cystinosis after renal failure. Pediatr Nephrol 1:260–268PubMed

Theodoropoulos DS, Krasnewich D, Kaiser-Kupfer MI, Gahl WA (1993) Classic nephropathic cystinosis as an adult disease. JAMA 270:2200–2204PubMed

Gahl WA, Thoene JG, Schneider JA, O’Regan S, Kaiser-Kupfer MI, Kuwabara T (1988) NIH conference. Cystinosis: progress in a prototypic disease. Ann Intern Med 109:557–569PubMed

Gahl W (2003) Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr 162[Suppl 1]:S38–41PubMed

10.

Thoene JG (1983) Cysteamine treatment of nephropathic cystinosis. Prog Clin Biol Res 127:125–131PubMed

11.

Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, Schlesselman JJ, Corden BJ, Schneider JA (1987) Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 316:971–977PubMed

12.

Markello TC, Bernardini IM, Gahl WA (1993) Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med 328:1157–1162PubMed

13.

Kimonis VE, Troendle J, Rose SR, Yang ML, Markello TC, Gahl WA (1995) Effects of early cysteamine therapy on thyroid function and growth in nephropathic cystinosis. J Clin Endocrinol Metab 80:3257–3261PubMed

14.

Sonies BC, Almajid P, Kleta R, Bernardini I, Gahl WA (2005) Swallowing dysfunction in 101 patients with nephropathic cystinosis: benefit of long-term cysteamine therapy. Medicine (Baltimore) 84:137–146

15.

Tsilou ET, Rubin BI, Reed G, Caruso RC, Iwata F, Balog J, Gahl WA, Kaiser-Kupfer MI (2006) Nephropathic cystinosis: posterior segment manifestations and effects of cysteamine therapy. Ophthalmology 113:1002–1009PubMed

16.

Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, Gahl WA (2004) Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr 145:555–560PubMed

17.

McDowell GA, Town MM, van’t Hoff W, Gahl WA (1998) Clinical and molecular aspects of nephropathic cystinosis. J Mol Med 76:295–302PubMed

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 (1998) Novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 18:319–324PubMed

19.

Kalatzis V, Cherqui S, Antignac C, Gasnier B (2001) Cystinosin, the protein defective in cystinosis, is a H+−driven lysosomal cystine transporter. EMBO J 20:5940–5949PubMedPubMedCentral

20.

Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, Guo J, Thoene J, Gahl WA (1998) CTNS mutations in an American-based population of cystinosis patients. Am J Hum Genet 63:1352–1362PubMedPubMedCentral

21.

McGowan-Jordan J, Stoddard K, Podolsky L, Orrbine E, McLaine P, Town M, Goodyer P, MacKenzie A, Heick H (1999) Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation. Eur J Hum Genet 7:671–678PubMed

22.

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 (2000) Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res 47:17–23PubMed

23.

Kleta R, Anikster Y, Lucero C, Shotelersuk V, Huizing M, Bernardini I, Park M, Thoene J, Schneider J, Gahl WA (2001) CTNS mutations in African American patients with cystinosis. Mol Genet Metab 74:332–337PubMed

24.

Kalatzis V, Antignac C (2002) Cystinosis: from gene to disease. Nephrol Dial Transplant 17:1883–1886PubMed

25.

Thoene J, Lemons R, Anikster Y, Mullet J, Paelicke K, Lucero C, Gahl W, Schneider J, Shu SG, Campbell HT (1999) Mutations of CTNS causing intermediate cystinosis. Mol Genet Metab 67:283–289PubMed

26.

Gahl WA, Bashan N, Tietze F, Bernardini I, Schulman JD (1982) Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science 217:1263–1265PubMed

27.

Gahl WA, Tietze F, Bashan N, Bernardini I, Raiford D, Schulman JD (1983) Characteristics of cystine counter-transport in normal and cystinotic lysosome-rich leucocyte granular fractions. Biochem J 216:393–400PubMedPubMedCentral

28.

Gahl WA, Bashan N, Tietze F, Schulman JD (1984) Lysosomal cystine counter-transport in heterozygotes for cystinosis. Am J Hum Genet 36:77–82

29.

Attard M, Jean G, Forestier L, Cherqui S, van’t Hoff W, Broyer M, Antignac C, Town M (1999) Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum Mol Genet 8:2507–2514PubMed

30.

Gahl WA, Tietze F (1987) Lysosomal cystine transport in cystinosis variants and their parents. Pediatr Res 21:193–196PubMed

31.

Park M, Helip-Wooley A, Thoene J (2002) Lysosomal cystine storage augments apoptosis in cultured human fibroblasts and renal tubular epithelial cells. J Am Soc Nephrol 13:2878–2887PubMed

32.

Guicciardi ME, Leist M, Gores GJ (2004) Lysosomes in cell death. Oncogene 23:2881–2890PubMed

33.

Racusen LC, Wilson PD, Hartz PA, Fivush BA, Burrow CR (1995) Renal proximal tubular epithelium from patients with nephropathic cystinosis: immortalized cell lines as in vitro model systems. Kidney Int 48:536–543PubMed

34.

Cherqui S, Sevin C, Hamard G, Kalatzis V, Sich M, Pequignot MO, Gogat K, Abitbol M, Broyer M, Gubler MC, Antignac C (2002) Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis. Mol Cell Biol 22:7622–7632PubMedPubMedCentral

35.

Lemire J, Kaplan BS (1984) The various renal manifestations of the nephropathic form of cystinosis. Am J Nephrol 4:81–85PubMed

36.

Baum M (1998) The Fanconi syndrome of cystinosis: insights into the pathophysiology. Pediatr Nephrol 12:492–497PubMed

37.

Arant BS, Greifer I, Edelmann CM Jr, Spitzer A (1976) Effect of chronic salt and water loading on the tubular defects of a child with Fanconi syndrome (cystinosis). Pediatrics 58:370–377PubMed

38.

Theodoropoulos DS, Shawker TH, Heinrichs C, Gahl WA (1995) Medullary nephrocalcinosis in nephropathic cystinosis. Pediatr Nephrol 9:412–418PubMed

39.

Gahl WA (1997) Nephropathic cystinosis. Pediatr Rev 18:302–304PubMed

40.

Bernardini I, Rizzo WB, Dalakas M, Bernar J, Gahl WA (1985) Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome. J Clin Invest 75:1124–1130PubMedPubMedCentral

41.

Ray TL, Tobias JD (2004) Perioperative care of the patient with nephropathic cystinosis. Paediatr Anaesth 14:878–885PubMed

42.

Langlois V, Geary D, Murray L, Champoux S, Hébert D, Goodyer P (2000) Polyuria and proteinuria in cystinosis have no impact on renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 15:7–10PubMed

43.

Pabico RC, Panner BJ, McKenna BA, Bryson MF (1980) Glomerular lesions in patients with late-onset cystinosis with massive proteinuria. Ren Physiol 3:347–354PubMed

44.

Middleton R, Bradbury M, Webb N, O’Donoghue D, Van’t Hoff W (2003) Cystinosis. A clinicopathological conference. “From toddlers to twenties and beyond” Adult-Paediatric Nephrology Interface Meeting, Manchester 2001. Nephrol Dial Transplant 18:2492–2495PubMed

45.

Gahl WA, Schneider JA, Schulman JD, Thoene JG, Reed GF (1990) Predicted reciprocal serum creatinine at age 10 years as a measure of renal function in children with nephropathic cystinosis treated with oral cysteamine. Pediatr Nephrol 4:129–135PubMed

46.

van’t Hoff WG, Ledermann SE, Waldron M, Trompeter RS (1995) Early-onset chronic renal failure as a presentation of infantile nephropathic cystinosis. Pediatr Nephrol 9:483–484

47.

Mahoney CP, Striker GE (2000) Early development of the renal lesions in infantile cystinosis. Pediatr Nephrol 15:50–56PubMed

48.

Koizumi F, Koeda T, Wakaki K, Matumoto M, Kobashi K, Akao T, Fukase M (1985) Cystinosis with marked atrophy of the kidneys and thyroid. Histological and ultrastructural studies in an autopsy case. Acta Pathol Jpn 35:145–155PubMed

49.

Burke JR, El-Bishti MM, Maisey MN, Chantler C (1978) Hypothyroidism in children with cystinosis. Arch Dis Child 53:947–951PubMedPubMedCentral

50.

Bercu BB, Orloff S, Schulman JD (1980) Pituitary resistance to thyroid hormone in cystinosis. J Clin Endocrinol Metab 51:1262–1268PubMed

51.

Betend B, Chatelain P, David L, François R (1982) Treatment of rickets caused by infantile cystinosis using 1 alpha-hydroxyvitamin D. Arch Fr Pediatr 39:615–618PubMed

52.

Zimakas PJ, Sharma AK, Rodd CJ (2003) Osteopenia and fractures in cystinotic children post renal transplantation. Pediatr Nephrol 18:384–390PubMed

53.

Wühl E, Haffner D, Offner G, Broyer M, van’t Hoff W, Mehls O (2001) European Study Group on Growth Hormone Treatment in Children with Nephropathic Cystinosis. Long-term treatment with growth hormone in short children with nephropathic cystinosis. J Pediatr 138:880–887PubMed

54.

Lucky AW, Howley PM, Megyesi K, Spielberg SP, Schulman JD (1977) Endocrine studies in cystinosis: compensated primary hypothyroidism. J Pediatr 91:204–210PubMed

55.

Chan AM, Lynch MJ, Bailey JD, Ezrin C, Fraser D (1970) Hypothyroidism in cystinosis. A clinical, endocrinologic and histologic study involving sixteen patients with cystinosis. Am J Med 48:678–692PubMed

56.

Broyer M, Tete MJ, Gubler MC (1987) Late symptoms in infantile cystinosis. Pediatr Nephrol 1:519–524PubMed

57.

Tsilou ET, Rubin BI, Reed GF, Iwata F, Gahl W, Kaiser-Kupfer MI (2002) Age-related prevalence of anterior segment complications in patients with infantile nephropathic cystinosis. Cornea 21:173–176PubMed

58.

Wong VG (1976) Ocular manifestations in cystinosis. Birth Defects Orig Arctic Ser 12:181–186

59.

Richard G, Kroll P (1983) Retinal changes in cystinosis. Ophthalmologica 186:211–218PubMed

60.

Dufier JL, Dhermy P, Gubler MC, Gagnadoux MF, Broyer M (1987) Ocular changes in long-term evolution of infantile cystinosis. Ophthalmic Paediatr Genet 8:131–137PubMed

61.

Gahl WA, Hubbard VS, Orloff S (1984) Decreased sweat production in cystinosis. J Pediatr 104:904–905PubMed

62.

Heller AN, Heller DS, Schwimmer A, Gordon RE, Cambria RJ (1994) Cystinosis and gingival hyperplasia: demonstration of cystine crystals in gingival tissue and unusual aspects of management. J Periodontol 65:1139–1141PubMed

63.

Busuttil DP, Liu Yin JA (2000) The bone marrow in hereditary cystinosis. Br J Haematol 111:385PubMed

64.

Olcay L, Erdemli E, Kesimer M, Büyükasik Y, Okur H, Kalkanoðlu HS, Coskun T, Altay C (2005) High cystine in platelets from patients with nephropathic cystinosis: a chemical, ultrastructural, and functional evaluation. J Clin Pathol 58:939–945PubMedPubMedCentral

65.

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 (2005) NIH Office of Rare Diseases. First NIH/Office of Rare Diseases Conference on cystinosis: past, present, and future. Pediatr Nephrol 20:452–454PubMed

66.

Thoene JG, Oshima RG, Crawhall JC, Olson DL, Schneider JA (1976) Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo. J Clin Invest 58:180–189PubMedPubMedCentral

67.

Pisoni RL, Thoene JG, Christensen HN (1985) Detection and characterization of carrier-mediated cationic amino acid transport in lysosomes of normal and cystinotic human fibroblasts: role in therapeutic cystine removal. J Biol Chem 260:4791–4798PubMed

68.

Gahl WA, Tietze F, Butler JD, Schulman JD (1985) Cysteamine depletes cystinotic leucocyte granular fractions of cystine by the mechanism of disulphide interchange. Biochem J 228:545–550PubMedPubMedCentral

69.

Kleta R, Gahl WA (2004) Pharmacological treatment of nephropathic cystinosis with cysteamine. Expert Opin Pharmacother 5:2255–2262PubMed

70.

Thoene JG (1995) Cystinosis. J Inherit Metab Dis 18:380–386PubMed

71.

da Silva VA, Zurbrugg RP, Lavanchy P, Blumberg A, Suter H, Wyss SR, Luthy CM, Oetliker OH (1985) Long-term treatment of infantile nephropathic cystinosis with cysteamine. N Engl J Med 313:1460–1463PubMed

72.

Gahl WA, Charnas L, Markello TC, Bernardini I, Ishak KG, Dalakas MC (1992) Parenchymal organ cystine depletion with long-term cysteamine therapy. Biochem Med Metab Biol 48:275–285PubMed

73.

Levtchenko EN, Wilmer M, de Graaf-Hess AC, van den Heuvel LP, Blom H, Monnens LA (2004) From gene to disease: cystinosis. Ned Tijdschr Geneeskd 148:476–478PubMed

74.

Kleta R, Gahl WA (2002) Cystinosis: antibodies and healthy bodies. J Am Soc Nephrol 13:2189–2191PubMed

75.

Dohil R, Fidler M, Barshop BA, Gangoiti J, Deutsch R, Martin M, Schneider JA (2006) Understanding intestinal cysteamine bitartrate absorption. J Pediatr 148:764–769PubMed

76.

Kleta R (2006) A deeper look into cysteamine absorption for the treatment of cystinosis. J Pediatr 148:718–719PubMed

77.

Vilaseca MA, Camacho JA, Briones P, Farré C, Mas A (1995) Biochemical follow-up in late-treated nephropathic cystinosis. J Inherit Metab Dis 18:147–150PubMed

78.

Kaiser-Kupfer MI, Fujikawa L, Kuwabara T, Jain S, Gahl WA (1987) Removal of corneal crystals by topical cysteamine in nephropathic cystinosis. N Engl J Med 316:775–779PubMed

79.

Kaiser-Kupfer MI, Gazzo MA, Datiles MB, Caruso RC, Kuehl EM, Gahl WA (1990) A randomized placebo-controlled trial of cysteamine eye drops in nephropathic cystinosis. Arch Ophthalmol 108:689–693PubMed

80.

Kaiser-Kupfer MI, Datiles MB, Gahl WA (1987) Corneal transplant in a boy with nephropathic cystinosis. Lancet 1:331PubMed

81.

Gahl WA, Schneider JA, Thoene JG, Chesney R (1986) Course of nephropathic cystinosis after age 10 years. J Pediatr 109:605–608PubMed

82.

Broyer M, Guillot M, Gubler MC, Habib R (1981) Infantile cystinosis: a reappraisal of early and late symptoms. Adv Nephrol Necker Hosp 10:137–166PubMed

83.

Gahl W, Balog J, Kleta R (2007) Nephropathic cystinosis in adults: natural history and effect of oral cysteamine therapy. Annals Intern Med 147:242–250

84.

Gahl WA, Dalakas MC, Charnas L, Chen KT, Pezeshkpour GH, Kuwabara T, Davis SL, Chesney RW, Fink J, Hutchison HT (1988) Myopathy and cystine storage in muscles in a patient with nephropathic cystinosis. N Engl J Med 319:1461–1464PubMed

85.

Charnas LR, Luciano CA, Dalakas M, Gilliatt RW, Bernardini I, Ishak K, Cwik VA, Fraker D, Brushart TA, Gahl WA (1994) Distal vacuolar myopathy in nephropathic cystinosis. Ann Neurol 35:181–188PubMed

86.

Müller-Felber W, Schröder M, Hirschmann M, Kastrup K, Töpfer M, Pongratz D (1999) Neurophysiological testing in long-standing cystinosis. Electromyogr Clin Neurophysiol 39:67–70PubMed

87.

Harper GS, Bernardini I, Hurko O, Zuurveld J, Gahl WA (1987) Cystine storage in cultured myotubes from patients with nephropathic cystinosis. Biochem J 243:841–845PubMedPubMedCentral

88.

Sonies BC, Ekman EF, Andersson HC, Adamson MD, Kaler SG, Markello TC, Gahl WA (1990) Swallowing dysfunction in nephropathic cystinosis. N Engl J Med 323:565–570PubMed

89.

Trauner DA, Fahmy RF, Mishler DA (2001) Oral motor dysfunction and feeding difficulties in nephropathic cystinosis. Pediatr Neurol 24:365–368PubMed

90.

Anikster Y, Lacbawan F, Brantly M, Gochuico BL, Avila NA, Travis W, Gahl WA (2001) Pulmonary dysfunction in adults with nephropathic cystinosis. Chest 119:394–401PubMed

91.

Broyer M, Tete MJ, Guest G, Bertheleme JP, Labrousse F, Poisson M (1996) Clinical polymorphism of cystinosis encephalopathy. Results of treatment with cysteamine. J Inherit Metab Dis 19:65–75PubMed

92.

Fink JK, Brouwers P, Barton N, Malekzadeh MH, Sato S, Hill S, Cohen WE, Fivush B, Gahl WA (1989) Neurologic complications in long-standing nephropathic cystinosis. Arch Neurol 46:543–548PubMed

93.

Levine S, Paparo G (1982) Brain lesions in a case of cystinosis. Acta Neuropathol (Berl) 57:217–220

94.

Cochat P, Drachman R, Gagnadoux MF, Pariente D, Broyer M (1986) Cerebral atrophy and nephropathic cystinosis. Arch Dis Child 61:401–403PubMedPubMedCentral

95.

Vogel DG, Malekzadeh MH, Cornford ME, Schneider JA, Shields WD, Vinters HV (1990) Central nervous system involvement in nephropathic cystinosis. J Neuropathol Exp Neurol 49:591–599PubMed

96.

Dogulu CF, Tsilou E, Rubin B, Fitzgibbon EJ, Kaiser-Kupper MI, Rennert OM, Gahl WA (2004) Idiopathic intracranial hypertension in cystinosis. J Pediatr 145:673–678PubMed

97.

Ross DL, Strife CF, Towbin R, Bove KE (1982) Nonabsorptive hydrocephalus associated with nephropathic cystinosis. Neurology 32:1330–1334PubMed

98.

Almond PS, Matas AJ, Nakhleh RE, Morel P, Troppmann C, Najarian JS, Chavers B (1993) Renal transplantation for infantile cystinosis: long-term follow-up. J Pediatr Surg 28:232–238PubMed

99.

Spilkin AM, Ballantyne AO, Babchuck LR, Trauner DA (2007) Non-verbal deficits in young children with a genetic metabolic disorder: WPPSI-III performance in cystinosis. Am J Med Genet B Neuropsychiatr Genet 144:444–447

100.

Ehrich JH, Wolff G, Stoeppler L, Heyer R, Offner G, Brodehl J (1979) Psychosocial intellectual development of children with infantile cystinosis and cerebral atrophy. Klin Padiatr 191:483–492PubMed

101.

Wolff G, Ehrich JH, Offner G, Brodehl J (1982) Psychosocial and intellectual development in 12 patients with infantile nephropathic cystinosis. Acta Paediatr Scand 71:1007–1011PubMed

102.

Colah S, Trauner DA (1997) Tactile recognition in infantile nephropathic cystinosis. Dev Med Child Neurol 39:409–413PubMed

103.

Ballantyne AO, Trauner DA (2000) Neurobehavioral consequences of a genetic metabolic disorder: visual processing deficits in infantile nephropathic cystinosis. Neuropsychiatry Neuropsychol Behav Neurol 13:254–263PubMed

104.

Nichols SL, Press GA, Schneider JA, Trauner DA (1990) Cortical atrophy and cognitive performance in infantile nephropathic cystinosis. Pediatr Neurol 6:379–381PubMed

105.

Delgado G, Schatz A, Nichols S, Appelbaum M, Trauner D (2005) Behavioral profiles of children with infantile nephropathic cystinosis. Dev Med Child Neurol 47:403–407PubMed

106.

Ueda M, O’Brien K, Rosing D, Ling A, Kleta R, McAreavey D, Bernardini I, Gahl W (2006) Coronary artery and other vascular calcifications in patients with cystinosis after kidney transplantation. Clin J Am Soc Nephrol 1:555–562PubMed

107.

Murphy JL, Papathakis PC (1993) Hypercholesterolemia in children with cystinosis. Pediatr Nephrol 7:159–162PubMed

108.

Dixit MP, Greifer I (2002) Nephropathic cystinosis associated with cardiomyopathy: a 27-year clinical follow-up. BMC Nephrol 3:8PubMedPubMedCentral

109.

Olgar S, Nisli K, Dindar A, Omeroglu RE, Ertugrul T (2006) Can cystinosis cause coronary artery dilatation? Pediatr Cardiol 27:263–268PubMed

110.

Strayer DS (1979) Cystinosis and dissecting aortic aneurysm in a 7-year-old boy. Am J Dis Child 133:436–438PubMed

111.

Winkler L, Offner G, Krull F, Brodehl J (1993) Growth and pubertal development in nephropathic cystinosis. Eur J Pediatr 152:244–249PubMed

112.

Chik CL, Friedman A, Merriam GR, Gahl WA (1993) Pituitary-testicular function in nephropathic cystinosis. Ann Intern Med 119:568–575PubMed

113.

Hillenbrand M, Stropahl G, Seiter H (1998) Massive tumour-like testicular cystine accumulation in a patient with infantile nephropathic cystinosis. Br J Urol 81:331–332PubMed

114.

Reiss RE, Kuwabara T, Smith ML, Gahl WA (1988) Successful pregnancy despite placental cystine crystals in a woman with nephropathic cystinosis. N Engl J Med 319:223–226PubMed

115.

Ammenti A, Grossi A, Bernasconi S (1986) Infantile cystinosis and insulin-dependent diabetes mellitus. Eur J Pediatr 145:548–549PubMed

116.

Fivush B, Green OC, Porter CC, Balfe JW, O’Regan S, Gahl WA (1987) Pancreatic endocrine insufficiency in posttransplant cystinosis. Am J Dis Child 141:1087–1089PubMed

117.

Filler G, Amendt P, von Bredow MA, Rohde W, Ehrich JH (1998) Slowly deteriorating insulin secretion and C-peptide production characterizes diabetes mellitus in infantile cystinosis. Eur J Pediatr 157:738–742PubMed

118.

Robert JJ, Tête MJ, Guest G, Gagnadoux MF, Niaudet P, Broyer M (1999) Diabetes mellitus in patients with infantile cystinosis after renal transplantation. Pediatr Nephrol 13:524–529PubMed

119.

Elenberg E, Norling LL, Kleinman RE, Ingelfinger JR (1998) Feeding problems in cystinosis. Pediatr Nephrol 12:365–370PubMed

120.

Avner ED, Ellis D, Jaffe R (1983) Veno-occlusive disease of the liver associated with cysteamine treatment of nephropathic cystinosis. J Pediatr 102:793–796PubMed

121.

O’Brien K, Hussain N, Warady BA, Kleiner DE, Kleta R, Bernardini I, Heller T, Gahl WA (2006) Nodular regenerative hyperplasia and severe portal hypertension in cystinosis. Clin Gastroenterol Hepatol 4:387–394PubMed

122.

Rossi S, Herrine SK, Navarro VJ (2005) Cystinosis as a cause of noncirrhotic portal hypertension. Dig Dis Sci 50:1372–1375PubMed

123.

DiDomenico P, Berry G, Bass D, Fridge J, Sarwal M (2004) Noncirrhotic portal hypertension in association with juvenile nephropathic cystinosis: case presentation and review of the literature. J Inherit Metab Dis 27:693–699PubMed

124.

Klenn PJ, Rubin R (1994) Hepatic fibrosis associated with hereditary cystinosis: a novel form of noncirrhotic portal hypertension. Mod Pathol 7:879–882PubMed

125.

Fivush B, Flick JA, Gahl WA (1988) Pancreatic exocrine insufficiency in a patient with nephropathic cystinosis. J Pediatr 112:49–51PubMed

126.

Treem WR, Rusnack EJ, Ragsdale BD, Seikaly MG, DiPalma JS (1988) Inflammatory bowel disease in a patient with nephropathic cystinosis. Pediatrics 81:584–587PubMed

127.

Assadi FK, Sandler RH, Wong PW, Salem M, Simenauer L (2002) Infantile cystinosis presenting as chronic constipation. Am J Kidney Dis 39:E24PubMed

128.

Kalatzis V, Serratrice N, Hippert C, Payet O, Arndt C, Cazevieille C, Maurice T, Hamel C, Malecaze F, Antignac C, Muller A, Kremer EJ (2007) The ocular anomalies in a cystinosis animal model mimic disease pathogenesis. Pediatr Res 62:156–162PubMed

129.

Geelen JM, Monnens LA, Levtchenko EN (2002) Follow-up and treatment of adults with cystinosis in the Netherlands. Nephrol Dial Transplant 17:1766–1770PubMed

130.

Levtchenko E, Blom H, Wilmer M, van den Heuvel L, Monnens L (2003) ACE inhibitor enalapril diminishes albuminuria in patients with cystinosis. Clin Nephrol 60:386–389PubMed

131.

Broyer M (2000) Cystinosis from childhood to adulthood. Nephrologie 21:13–18PubMed

132.

Beckman DA, Mullin JJ, Assadi FK (1998) Developmental toxicity of cysteamine in the rat: effects on embryo-fetal development. Teratology 58:96–102PubMed

133.

Haase M, Morgera S, Bamberg C, Halle H, Martini S, Dragun D, Neumayer H-H, Budde K (2006) Successful pregnancies in dialysis patients including those suffering from cystinosis and familial Mediterranean fever. J Nephrol 19:677–681PubMed

Title: Nephropathic cystinosis: late complications of a multisystemic disease
Authors: Galina Nesterova
William Gahl
Publication date: 01-06-2008
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 6/2008
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-007-0650-8

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Springer Medicine

Nephropathic cystinosis: late complications of a multisystemic disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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