title: A potential new method to estimate tissue cystine content in nephropathic cystinosis.
abstract: OBJECTIVE
  To evaluate intestinal mucosal cystine crystal (CC) load as a way to estimate tissue cystine content in children with cystinosis.
  
  
  METHODS
  Intestinal mucosal biopsies were obtained endoscopically from children (ages 2-18 years) with cystinosis. Using a special processing technique, CC within histiocytes were easily visible and enumerable in the mucosal tissue. Mean CC counts, calculated from stomach and duodenum combined (CC-GD), were correlated with duration of cysteamine treatment, estimated glomerular filtration rate (eGFR), and mean white blood cells (WBC) cystine levels.
  
  
  RESULTS
  Seventeen subjects (6 male) were enrolled in 2 studies from 2001 and 2003. The CC-GD count (mean 12.5 ± 1.41 crystals/histiocyte) was lower than the colonic crystal count (mean 23.6 ± 3.38, P = .0031). Nine of 17 subjects underwent repeated endoscopy 2 years later and the trend for CC-GD was to decrease over time (P = .065). Biopsies, however, were never completely depleted of CC. In subjects who were diagnosed before age 18 months, the percent change from baseline of both eGFR and CC-GD were inversely correlated (P = .026). Mean WBC cystine levels were positively correlated with CC-GD (P = .023).
  
  
  CONCLUSIONS
  CC are easily visible in the intestinal mucosa. CC-GD counts appear to correlate with eGFR and may help monitor response to treatment. Even when mean WBC cystine levels are low, the mucosal CC are not depleted suggesting that tissue cysteamine levels may not achieve therapeutic efficacy.
authors.affiliation: Departments of Pediatrics and Pathology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dohil
authors.forename: Alison
authors.initials: A
authors.lastname: Carrigg
authors.forename: Robert
authors.initials: R
authors.lastname: Newbury
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003460:Crystallization; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000378:metabolism*; D016099:Endoscopy, Gastrointestinal; D005198:Fanconi Syndrome / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D006644:Histiocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D012812:Sigmoidoscopy
chemical_list: D003553:Cystine