title: Muscle carnitine repletion by long-term carnitine supplementation in nephropathic cystinosis.
abstract: The renal tubular Fanconi syndrome of children with nephropathic cystinosis causes plasma and muscle carnitine depletion. L-Carnitine replacement therapy for up to 18 mo has previously been shown to normalize plasma but not muscle carnitine levels. We treated six cystinosis patients, aged 1 to 4 y, with a mean dosage of 92 mg L-carnitine/kg/d given every 6 h for an average of 62 mo. Despite fractional excretions of free carnitine ranging from 55 to 108%, plasma-free and total carnitine concentrations were maintained at or above normal levels. At the end of the carnitine replacement period, the six children had muscle-free carnitine values ranging from 16.0 to 28.0 nmol/mg noncollagen protein compared with values of 3.0 to 11.4 for cystinosis children not supplemented with carnitine [normal, 22.7 +/- 5.0 (SD) nmol/mg protein]. Total muscle carnitine values were also normalized by L-carnitine replacement. The monthly increase in total body creatinine production, a measure of muscle mass, was higher (p = 0.036) in children with normal plasma free carnitine concentrations (3.4 +/- 0.9 mg/d) than in children with low plasma free carnitine (2.3 +/- 0.7 mg/d). No serious side effects, such as severe diarrhea, were observed. We conclude that oral L-carnitine replacement can normalize muscle carnitine content in children with cystinosis.
authors.affiliation: Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
authors.forename: I M
authors.initials: IM
authors.lastname: Bernardini
authors.forename: M C
authors.initials: MC
authors.lastname: Dalakas
authors.forename: T C
authors.initials: TC
authors.lastname: Markello
authors.forename: D M
authors.initials: DM
authors.lastname: Krasnewich
authors.forename: L R
authors.initials: LR
authors.lastname: Charnas
mesh_terms: D002331:Carnitine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003554:Cystinosis / Q000188:drug therapy* / Q000378:metabolism*; D004334:Drug Administration Schedule; D005198:Fanconi Syndrome / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007223:Infant; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002331:Carnitine