Nephropathic Cystinosis: an International Consensus Document

Overview

Journal Nephrol Dial Transplant

Publisher Oxford University Press

Specialties General Surgery
Nephrology

Date 2014 Aug 29

PMID 25165189

Citations 83

Authors

Francesco Emma

Galina Nesterova

Craig Langman

Antoine Labbe

Stephanie Cherqui

Paul Goodyer

Mirian C Janssen

Marcella Greco

Rezan Topaloglu

Ewa Elenberg

Ranjan Dohil

Doris Trauner

Corinne Antignac

Pierre Cochat

Frederick Kaskel

Aude Servais

Elke Wuhl

Patrick Niaudet

William Vant Hoff

William Gahl

Elena Levtchenko

Affiliations

Soon will be listed here.

Abstract

Cystinosis is caused by mutations in the CTNS gene (17p13.2), which encodes for a lysosomal cystine/proton symporter termed cystinosin. It is the most common cause of inherited renal Fanconi syndrome in young children. Because of its rarity, the diagnosis and specific treatment of cystinosis are frequently delayed, which has a significant impact on the overall prognosis. In this document, we have summarized expert opinions on several aspects of the disease to improve knowledge and provide guidance for diagnosis and treatment.

Citing Articles

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References

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. DOI: 10.1093/hmg/ddh152. View

Kleta R, Bernardini I, Ueda M, Varade W, Phornphutkul C, Krasnewich D . Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr. 2004; 145(4):555-60. DOI: 10.1016/j.jpeds.2004.03.056. View

Gahl W, Reed G, Thoene J, Schulman J, Rizzo W, Jonas A . Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med. 1987; 316(16):971-7. DOI: 10.1056/NEJM198704163161602. View

Broyer M, Tete M, Gubler M . Late symptoms in infantile cystinosis. Pediatr Nephrol. 1987; 1(3):519-24. DOI: 10.1007/BF00849263. View

van Stralen K, Emma F, Jager K, Verrina E, Schaefer F, Laube G . Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol. 2011; 6(10):2485-91. PMC: 3359556. DOI: 10.2215/CJN.02000311. View

Forestier L, Jean G, Attard M, Cherqui S, Lewis C, Vant Hoff W . Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay. Am J Hum Genet. 1999; 65(2):353-9. PMC: 1377934. DOI: 10.1086/302509. View

Gaide Chevronnay H, Janssens V, Van Der Smissen P, NKuli F, Nevo N, Guiot Y . Time course of pathogenic and adaptation mechanisms in cystinotic mouse kidneys. J Am Soc Nephrol. 2014; 25(6):1256-69. PMC: 4033369. DOI: 10.1681/ASN.2013060598. View

Sonies B, Almajid P, Kleta R, Bernardini I, Gahl W . Swallowing dysfunction in 101 patients with nephropathic cystinosis: benefit of long-term cysteamine therapy. Medicine (Baltimore). 2005; 84(3):137-146. DOI: 10.1097/01.md.0000164204.00159.d4. View

vant Hoff W, Gretz N . The treatment of cystinosis with cysteamine and phosphocysteamine in the United Kingdom and Eire. Pediatr Nephrol. 1995; 9(6):685-9. DOI: 10.1007/BF00868711. View

10.

Wuhl E, Haffner D, Offner G, Broyer M, Vant Hoff W, Mehls O . Long-term treatment with growth hormone in short children with nephropathic cystinosis. J Pediatr. 2001; 138(6):880-7. DOI: 10.1067/mpd.2001.113263. View

11.

Bava S, Theilmann R, Sach M, May S, Frank L, Hesselink J . Developmental changes in cerebral white matter microstructure in a disorder of lysosomal storage. Cortex. 2009; 46(2):206-16. PMC: 3351112. DOI: 10.1016/j.cortex.2009.03.008. View

12.

Wilmer M, Schoeber J, Van den Heuvel L, Levtchenko E . Cystinosis: practical tools for diagnosis and treatment. Pediatr Nephrol. 2010; 26(2):205-15. PMC: 3016220. DOI: 10.1007/s00467-010-1627-6. View

13.

Wilmer M, Kluijtmans L, van der Velden T, Willems P, Scheffer P, Masereeuw R . Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim Biophys Acta. 2011; 1812(6):643-51. DOI: 10.1016/j.bbadis.2011.02.010. View

14.

Park M, Helip-Wooley A, Thoene J . Lysosomal cystine storage augments apoptosis in cultured human fibroblasts and renal tubular epithelial cells. J Am Soc Nephrol. 2002; 13(12):2878-87. DOI: 10.1097/01.asn.0000036867.49866.59. View

15.

Reiss R, Kuwabara T, Smith M, Gahl W . Successful pregnancy despite placental cystine crystals in a woman with nephropathic cystinosis. N Engl J Med. 1988; 319(4):223-6. DOI: 10.1056/NEJM198807283190406. View

16.

Dohil R, Carrigg A, Newbury R . A potential new method to estimate tissue cystine content in nephropathic cystinosis. J Pediatr. 2012; 161(3):531-535.e1. DOI: 10.1016/j.jpeds.2012.03.011. View

17.

Taranta A, Petrini S, Citti A, Boldrini R, Corallini S, Bellomo F . Distribution of cystinosin-LKG in human tissues. Histochem Cell Biol. 2012; 138(2):351-63. DOI: 10.1007/s00418-012-0958-8. View

18.

SPEAR G, Gubler M, Habib R, Broyer M . Renal allografts in cystinosis and mesangial demography. Clin Nephrol. 1989; 32(6):256-61. View

19.

Nesterova G, Gahl W . Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2007; 23(6):863-78. DOI: 10.1007/s00467-007-0650-8. View

20.

Park M, Pejovic V, Kerisit K, Junius S, Thoene J . Increased apoptosis in cystinotic fibroblasts and renal proximal tubule epithelial cells results from cysteinylation of protein kinase Cdelta. J Am Soc Nephrol. 2006; 17(11):3167-75. DOI: 10.1681/ASN.2006050474. View