title: C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man.
abstract: X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demyelinating disease (cerebral ALD). Hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. Unfortunately, this narrow therapeutic window is often missed. Therefore, an increasing number of newborn screening programs are including ALD. To identify new biomarkers for ALD, we developed an Abcd1 knockout mouse with enhanced VLCFA synthesis either ubiquitous or restricted to oligodendrocytes. Biochemical analysis revealed VLCFA accumulation in different lipid classes and acylcarnitines. Both C26:0-lysoPC and C26:0-carnitine were highly elevated in brain, spinal cord, but also in bloodspots. We extended the analysis to patients and confirmed that C26:0-carnitine is also elevated in bloodspots from ALD patients. We anticipate that validation of C26:0-carnitine for the diagnosis of ALD in newborn bloodspots may lead to a faster inclusion of ALD in newborn screening programs in countries that already screen for other inborn errors of metabolism.
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Malu-Clair
authors.initials: MC
authors.lastname: van de Beek
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Inge M E
authors.initials: IM
authors.lastname: Dijkstra
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: van Lenthe
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Ofman
authors.affiliation: Metabolomic Discoveries GmbH, Potsdam-Golm, Germany.
authors.forename: Dalia
authors.initials: D
authors.lastname: Goldhaber-Pasillas
authors.affiliation: Metabolomic Discoveries GmbH, Potsdam-Golm, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schauer
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Schackmann
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Engelen-Lee
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Kulik
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.affiliation: Departments of Pediatrics and Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Engelen
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Departments of Pediatrics and Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kemp
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000123:Acetyltransferases / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000175:diagnosis* / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D042241:Early Diagnosis; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism; D055879:Gene Knock-In Techniques; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; C552836:Abcd1 protein, mouse; D015415:Biomarkers; D005227:Fatty Acids; D008244:Lysophosphatidylcholines; C116917:acylcarnitine; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D002331:Carnitine