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Published in: CEN Case Reports 1/2018

01-05-2018 | Case Report

Slow progression of renal failure in a child with infantile cystinosis

Authors: Maria Bitsori, Eleni Vergadi, Emmanouil Galanakis

Published in: CEN Case Reports | Issue 1/2018

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Abstract

Cystinosis is a rare autosomal recessive lysosomal transport disorder, characterized by the accumulation of the aminoacid cystine and progressive dysfunction of several organs. Kidneys are severely affected, and the most frequent form, infantile nephropathic cystinosis, presents with growth failure in infancy, renal Fanconi syndrome and end-stage renal disease by the first decade of life. We report of a girl with infantile nephropathic cystinosis that has reached adolescence without the need of renal replacement therapy and without extrarenal manifestations despite her delayed diagnosis and treatment initiation. The girl with this intermediate phenotype was found to have compound heterozygosity of one known (1015G > A) and one novel (587_588insA) mutation in CTNS gene. Our case points to the wide clinical presentation of infantile nephropathic cystinosis and suggest that long-term outcome is not always ominous as generally thought.
Literature
1.
go back to reference Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2013;28:51–9.CrossRefPubMed Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2013;28:51–9.CrossRefPubMed
2.
go back to reference Emma F, Nesterova G, Langman C, Labbe A, Cherqui S, Goodyer P, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transpl. 2014;29(Suppl 4):iv87–94.CrossRef Emma F, Nesterova G, Langman C, Labbe A, Cherqui S, Goodyer P, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transpl. 2014;29(Suppl 4):iv87–94.CrossRef
4.
go back to reference Servais A, Moriniere V, Grunfeld JP, Noel LH, Goujon JM, Chadefaux-Vekemans B, Antignac C. Late-onset nephropathic cystinosis: clinical presentation, outcome, and genotyping. Clin J Am Soc Nephrol. 2008;3:27–35.CrossRefPubMedPubMedCentral Servais A, Moriniere V, Grunfeld JP, Noel LH, Goujon JM, Chadefaux-Vekemans B, Antignac C. Late-onset nephropathic cystinosis: clinical presentation, outcome, and genotyping. Clin J Am Soc Nephrol. 2008;3:27–35.CrossRefPubMedPubMedCentral
5.
go back to reference Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser-Kupfer MI. Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol Genet Metab. 2000;71:100–20.CrossRefPubMed Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser-Kupfer MI. Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol Genet Metab. 2000;71:100–20.CrossRefPubMed
6.
go back to reference Nesterova G, Gahl W. Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2008;23:863–78.CrossRefPubMed Nesterova G, Gahl W. Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2008;23:863–78.CrossRefPubMed
7.
go back to reference Gahl WA. Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr. 2003;162(Suppl 1):S38–41.CrossRefPubMed Gahl WA. Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr. 2003;162(Suppl 1):S38–41.CrossRefPubMed
8.
go back to reference Greco M, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr Nephrol. 2010;25:2459–67.CrossRefPubMed Greco M, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr Nephrol. 2010;25:2459–67.CrossRefPubMed
9.
go back to reference Touchman JW, Anikster Y, Dietrich NL, Maduro VV, McDowell G, Shotelersuk V, et al. The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion. Genome Res. 2000;10:165–73.CrossRefPubMedPubMedCentral Touchman JW, Anikster Y, Dietrich NL, Maduro VV, McDowell G, Shotelersuk V, et al. The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion. Genome Res. 2000;10:165–73.CrossRefPubMedPubMedCentral
10.
go back to reference Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet. 1998;18:319–24.CrossRefPubMed Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet. 1998;18:319–24.CrossRefPubMed
11.
go back to reference Anikster Y, Lucero C, Touchman JW, Huizing M, McDowell G, Shotelersuk V, et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol Genet Metab. 1999;66:111–6.CrossRefPubMed Anikster Y, Lucero C, Touchman JW, Huizing M, McDowell G, Shotelersuk V, et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol Genet Metab. 1999;66:111–6.CrossRefPubMed
12.
go back to reference Attard M, Jean G, Forestier L, Cherqui S, van’t Hoff W, Broyer M, et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum Mol Genet. 1999;8:2507–14.CrossRefPubMed Attard M, Jean G, Forestier L, Cherqui S, van’t Hoff W, Broyer M, et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum Mol Genet. 1999;8:2507–14.CrossRefPubMed
13.
go back to reference Kalatzis V, Cohen-Solal L, Cordier B, Frishberg Y, Kemper M, Nuutinen EM, et al. Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis. Hum Mutat. 2002;20:439–46.CrossRefPubMed Kalatzis V, Cohen-Solal L, Cordier B, Frishberg Y, Kemper M, Nuutinen EM, et al. Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis. Hum Mutat. 2002;20:439–46.CrossRefPubMed
14.
go back to reference Thoene J, Lemons R, Anikster Y, Mullet J, Paelicke K, Lucero C, et al. Mutations of CTNS causing intermediate cystinosis. Mol Genet Metab. 1999;67:283–93.CrossRefPubMed Thoene J, Lemons R, Anikster Y, Mullet J, Paelicke K, Lucero C, et al. Mutations of CTNS causing intermediate cystinosis. Mol Genet Metab. 1999;67:283–93.CrossRefPubMed
15.
go back to reference Emma F, Bertini E, Salviati L, Montini G. Renal involvement in mitochondrial cytopathies. Pediatr Nephrol. 2012;27:539–50.CrossRefPubMed Emma F, Bertini E, Salviati L, Montini G. Renal involvement in mitochondrial cytopathies. Pediatr Nephrol. 2012;27:539–50.CrossRefPubMed
16.
go back to reference Haque SK, Ariceta G, Batlle D. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies. Nephrol Dial Transpl. 2012;27:4273–87.CrossRef Haque SK, Ariceta G, Batlle D. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies. Nephrol Dial Transpl. 2012;27:4273–87.CrossRef
18.
go back to reference Higashi S, Matsunoshita N, Otani M, Tokuhiro E, Nozu K, Ito S. Diagnostic challenge in a patient with nephropathic juvenile cystinosis: a case report. BMC Nephrol. 2017;18:300.CrossRefPubMedPubMedCentral Higashi S, Matsunoshita N, Otani M, Tokuhiro E, Nozu K, Ito S. Diagnostic challenge in a patient with nephropathic juvenile cystinosis: a case report. BMC Nephrol. 2017;18:300.CrossRefPubMedPubMedCentral
19.
go back to reference Mochizuki H, Joh K, Kawame H, Imadachi A, Nozaki H, Ohashi T, et al. Mitochondrial encephalomyopathies preceded by de-toni-debre-fanconi syndrome or focal segmental glomerulosclerosis. Clin Nephrol. 1996;46:347–52.PubMed Mochizuki H, Joh K, Kawame H, Imadachi A, Nozaki H, Ohashi T, et al. Mitochondrial encephalomyopathies preceded by de-toni-debre-fanconi syndrome or focal segmental glomerulosclerosis. Clin Nephrol. 1996;46:347–52.PubMed
20.
go back to reference Wilmer MJ, van den Heuvel LP, Rodenburg RJ, Vogel RO, Nijtmans LG, Monnens LA, Levtchenko EN. Mitochondrial complex v expression and activity in cystinotic fibroblasts. Pediatr Res. 2008;64:495–7.CrossRefPubMed Wilmer MJ, van den Heuvel LP, Rodenburg RJ, Vogel RO, Nijtmans LG, Monnens LA, Levtchenko EN. Mitochondrial complex v expression and activity in cystinotic fibroblasts. Pediatr Res. 2008;64:495–7.CrossRefPubMed
21.
go back to reference Levtchenko EN, Wilmer MJ, Janssen AJ, Koenderink JB, Visch HJ, Willems PH, et al. Decreased intracellular atp content and intact mitochondrial energy generating capacity in human cystinotic fibroblasts. Pediatr Res. 2006;59:287–92.CrossRefPubMed Levtchenko EN, Wilmer MJ, Janssen AJ, Koenderink JB, Visch HJ, Willems PH, et al. Decreased intracellular atp content and intact mitochondrial energy generating capacity in human cystinotic fibroblasts. Pediatr Res. 2006;59:287–92.CrossRefPubMed
22.
go back to reference Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L, Wong LJ, Sarwal MM. Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis. J Am Soc Nephrol. 2010;21:272–83.CrossRefPubMedPubMedCentral Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L, Wong LJ, Sarwal MM. Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis. J Am Soc Nephrol. 2010;21:272–83.CrossRefPubMedPubMedCentral
23.
go back to reference Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, et al. Genetic basis of cystinosis in turkish patients: a single-center experience. Pediatr Nephrol. 2012;27:115–21.CrossRefPubMed Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, et al. Genetic basis of cystinosis in turkish patients: a single-center experience. Pediatr Nephrol. 2012;27:115–21.CrossRefPubMed
24.
go back to reference Van Stralen KJ, Emma F, Jager KJ, Verrina E, Schaefer F, Laube GF, et al. Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol. 2011;6:2485–91.CrossRefPubMedPubMedCentral Van Stralen KJ, Emma F, Jager KJ, Verrina E, Schaefer F, Laube GF, et al. Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol. 2011;6:2485–91.CrossRefPubMedPubMedCentral
25.
go back to reference Anikster Y, Lucero C, Guo J, Huizing M, Shotelersuk V, Bernardini I, et al. Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res. 2000;47:17–23.CrossRefPubMed Anikster Y, Lucero C, Guo J, Huizing M, Shotelersuk V, Bernardini I, et al. Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res. 2000;47:17–23.CrossRefPubMed
26.
go back to reference Kiehntopf M, Schickel J, Gonne B, Koch HG, Superti-Furga A, Steinmann B, et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum Mutat. 2002;20:237.CrossRefPubMed Kiehntopf M, Schickel J, Gonne B, Koch HG, Superti-Furga A, Steinmann B, et al. Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis. Hum Mutat. 2002;20:237.CrossRefPubMed
27.
go back to reference Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, et al. CTNS mutations in an american-based population of cystinosis patients. Am J Hum Genet. 1998;63:1352–62.CrossRefPubMedPubMedCentral Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, et al. CTNS mutations in an american-based population of cystinosis patients. Am J Hum Genet. 1998;63:1352–62.CrossRefPubMedPubMedCentral
28.
go back to reference Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C. Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet. 2004;13(13):1361–71.CrossRefPubMed Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C. Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet. 2004;13(13):1361–71.CrossRefPubMed
29.
go back to reference Rupar CA, Matsell D, Surry S, Siu V. A G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western ontario amish mennonite population. J Med Genet. 2001;38:615–6.CrossRefPubMedPubMedCentral Rupar CA, Matsell D, Surry S, Siu V. A G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western ontario amish mennonite population. J Med Genet. 2001;38:615–6.CrossRefPubMedPubMedCentral
30.
go back to reference Chiaverini C, Sillard L, Flori E, Ito S, Briganti S, Wakamatsu K, et al. Cystinosin is a melanosomal protein that regulates melanin synthesis. Faseb J. 2012;26:3779–89.CrossRefPubMed Chiaverini C, Sillard L, Flori E, Ito S, Briganti S, Wakamatsu K, et al. Cystinosin is a melanosomal protein that regulates melanin synthesis. Faseb J. 2012;26:3779–89.CrossRefPubMed
Metadata
Title
Slow progression of renal failure in a child with infantile cystinosis
Authors
Maria Bitsori
Eleni Vergadi
Emmanouil Galanakis
Publication date
01-05-2018
Publisher
Springer Japan
Published in
CEN Case Reports / Issue 1/2018
Electronic ISSN: 2192-4449
DOI
https://doi.org/10.1007/s13730-018-0316-3

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