title: Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome.
abstract: 11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-[3H]carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined.
authors.affiliation: Section of Human Biochemical Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
authors.forename: I
authors.initials: I
authors.lastname: Bernardini
authors.forename: M
authors.initials: M
authors.lastname: Dalakas
authors.forename: W B
authors.initials: WB
authors.lastname: Rizzo
authors.forename: G S
authors.initials: GS
authors.lastname: Harper
authors.forename: J M
authors.initials: JM
authors.lastname: Hoeg
authors.forename: O
authors.initials: O
authors.lastname: Hurko
authors.forename: J
authors.initials: J
authors.lastname: Bernar
mesh_terms: D000284:Administration, Oral; D001692:Biological Transport; D002331:Carnitine / Q000008:administration & dosage* / Q000172:deficiency / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D003543:Cysteamine / Q000494:pharmacology; D003554:Cystinosis / Q000188:drug therapy*; D005198:Fanconi Syndrome / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation; D050356:Lipid Metabolism; D008657:Metabolic Clearance Rate; D009132:Muscles / Q000378:metabolism; D009800:Oculocerebrorenal Syndrome / Q000188:drug therapy*; D015499:Renal Tubular Transport, Inborn Errors / Q000188:drug therapy*; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D003543:Cysteamine; D002784:Cholesterol; D002331:Carnitine