title: Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis.
abstract: Cystinosis is an autosomal recessive disorder, caused by mutations in the lysosomal cystine carrier cystinosin, encoded by the CTNS gene. The disease generally manifests with Fanconi syndrome during the first year of life and progresses towards end stage renal disease before the age of 10 years. Cysteamine depletes intralysosomal cystine content, postpones the deterioration of renal function and the occurrence of extra-renal organ damage. Based on the pharmacokinetic data, patients with cystinosis are advised to use cysteamine every 6 h. The aim of this study was (1) to evaluate the cysteamine dose regimen in Dutch patients with cystinosis and (2) to determine morning polymorphonuclear (PMN) leukocyte cystine content 6 h vs 9 h after the last evening cysteamine dose. Only 5/22 of Dutch cystinosis patients ingested cysteamine every 6 h. Morning (8 a.m.) PMN cystine content in 11 examined patients was elevated 9 h after 12.5-15 mg/kg evening cysteamine dose compared to the value 6 h after the ingestion of the same dose (0.73+/-0.81 nmol vs 0.44+/-0.52 nmol cystine/mg protein, p =0.02). In conclusion, only the minority of Dutch cystinosis patients follows the recommended strict cysteamine dose regimen. We provide evidence that cysteamine has to be administered every 6 h, including the night, as it has much better effect for maintaining low PMN cystine levels.
authors.affiliation: Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, P.O. 9101, 6500 HB, Nijmegen, The Netherlands. e.levtchenko@cukz.umcn.nl
authors.forename: Elena N
authors.initials: EN
authors.lastname: Levtchenko
authors.forename: Carin M
authors.initials: CM
authors.lastname: van Dael
authors.forename: Addy C
authors.initials: AC
authors.lastname: de Graaf-Hess
authors.forename: Martijn J G
authors.initials: MJ
authors.lastname: Wilmer
authors.forename: Lambertus P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Leo A
authors.initials: LA
authors.lastname: Monnens
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
mesh_terms: D000293:Adolescent; D002648:Child; D003543:Cysteamine / Q000008:administration & dosage* / Q000032:analysis; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000378:metabolism* / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000737:chemistry; D013997:Time Factors
chemical_list: D003553:Cystine; D003543:Cysteamine