Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy.

Autor: Huffnagel IC; Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., van de Beek MC; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Showers AL; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA., Orsini JJ; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA., Klouwer FCC; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Dijkstra IME; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Schielen PC; Center for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, Bilthoven, The Netherlands., van Lenthe H; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Wanders RJA; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Vaz FM; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Morrissey MA; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA., Engelen M; Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Kemp S; Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: s.kemp@amc.uva.nl.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2017 Dec; Vol. 122 (4), pp. 209-215. Date of Electronic Publication: 2017 Oct 28.
DOI: 10.1016/j.ymgme.2017.10.012
Abstrakt: X-linked adrenoleukodystrophy (ALD) is the most common leukodystrophy with a birth incidence of 1:14,700 live births. The disease is caused by mutations in ABCD1 and characterized by very long-chain fatty acids (VLCFA) accumulation. In childhood, male patients are at high-risk to develop adrenal insufficiency and/or cerebral demyelination. Timely diagnosis is essential. Untreated adrenal insufficiency can be life-threatening and hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. For this reason, ALD is being added to an increasing number of newborn screening programs. ALD newborn screening involves the quantification of C26:0-lysoPC in dried blood spots which requires a dedicated method. C26:0-carnitine, that was recently identified as a potential new biomarker for ALD, has the advantage that it can be added as one more analyte to the routine analysis of amino acids and acylcarnitines already in use. The first objective of this study was a comparison of the sensitivity of C26:0-carnitine and C26:0-lysoPC in dried blood spots from control and ALD newborns both in a case-control study and in newborns included in the New York State screening program. While C26:0-lysoPC was elevated in all ALD newborns, C26:0-carnitine was elevated only in 83%. Therefore, C26:0-carnitine is not a suitable biomarker to use in ALD newborn screen. In women with ALD, plasma VLCFA analysis results in a false negative result in approximately 15-20% of cases. The second objective of this study was to compare plasma VLCFA analysis with C26:0-carnitine and C26:0-lysoPC in dried blood spots of women with ALD. Our results show that C26:0-lysoPC was elevated in dried blood spots from all women with ALD, including from those with normal plasma C26:0 levels. This shows that C26:0-lysoPC is a better and more accurate biomarker for ALD than plasma VLCFA levels. We recommend that C26:0-lysoPC be added to the routine biochemical array of diagnostic tests for peroxisomal disorders.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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