title: Copper deficiency in patients with cystinosis with cysteamine toxicity.
abstract: OBJECTIVE
  To assess whether copper deficiency plays a role in the recently described cysteamine toxicity in patients with cystinosis, and to examine whether polymorphisms in copper transporters, lysyl oxidase, and/or type I procollagen genes could be responsible for the occurrence of cysteamine toxicity in a small subset of patients with cystinosis.
  
  
  METHODS
  Thirty-six patients with cystinosis were included: 22 with Fanconi syndrome (including 7 with cysteamine toxicity), 12 after renal transplantation, 1 receiving hemodialysis, and 1 with ocular cystinosis. Serum copper and ceruloplasmin levels and urinary copper/creatinine ratio were measured. Genes ATP7A and CTR1 (encoding copper transporters), LOX (encoding lysyl oxidase), and COL1A1 and COL1A2 (encoding type I procollagen) were analyzed in patients with (n = 6) and without (n = 5) toxicity. Fibroblast (pro)collagen synthesis was compared in patients with (n = 3) and those without (n = 2) cysteamine toxicity.
  
  
  RESULTS
  All 22 patients with Fanconi syndrome had increased urinary copper excretion. Serum copper and ceruloplasmin levels were decreased in 9 patients, including all 7 patients with cysteamine toxicity. No specific sequence variations were associated with toxicity. All fibroblasts exhibited normal (pro)collagen synthesis.
  
  
  CONCLUSIONS
  Patients with cystinosis with cysteamine toxicity demonstrate copper deficiency. This can cause decreased activity of lysyl oxidase, the enzyme that generates the aldehydes required for collagen cross-linking. Thus, copper supplementation might prevent cysteamine toxicity.
authors: Department of Pediatric Nephrology, Leuven University Hospital, Leuven, Belgium. martine.besouw@uzleuven.be
authors: Martine T P
authors: MT
authors: Besouw
authors: Jerry
authors: J
authors: Schneider
authors: Mirian C
authors: MC
authors: Janssen
authors: Marcella
authors: M
authors: Greco
authors: Francesco
authors: F
authors: Emma
authors: Elisabeth A
authors: EA
authors: Cornelissen
authors: Koen
authors: K
authors: Desmet
authors: Flemming
authors: F
authors: Skovby
authors: François
authors: F
authors: Nobili
authors: Marc R
authors: MR
authors: Lilien
authors: Anne
authors: A
authors: De Paepe
authors: Fransiska
authors: F
authors: Malfait
authors: Sofie
authors: S
authors: Symoens
authors: Lambertus P
authors: LP
authors: van den Heuvel
authors: Elena N
authors: EN
authors: Levtchenko
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D003543:Cysteamine / Q000009:adverse effects* / Q000627:therapeutic use; D003554:Cystinosis / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005198:Fanconi Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020011:Protective Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D012076:Renal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D000079923:Copper Transporter 1; D005819:Genetic Markers; D020011:Protective Agents; D012076:Renal Agents; C490079:SLC31A1 protein, human; D003543:Cysteamine; D003300:Copper; D003094:Collagen; D002570:Ceruloplasmin; D008249:Protein-Lysine 6-Oxidase; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases
keywords: FS; Fanconi syndrome