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

Irene C Huffnagel; Malu-Clair van de Beek; Amanda L Showers; Joseph J Orsini; Femke C C Klouwer; Inge M E Dijkstra; Peter C Schielen; Henk van Lenthe; Ronald J A Wanders; Frédéric M Vaz; Mark A Morrissey; Marc Engelen; Stephan Kemp

doi:10.1016/j.ymgme.2017.10.012

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

Mol Genet Metab. 2017 Dec;122(4):209-215. doi: 10.1016/j.ymgme.2017.10.012. Epub 2017 Oct 28.

Affiliations

¹ 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.
² 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.
³ Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
⁴ 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.
⁵ Center for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
⁶ 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.

PMID: 29089175
DOI: 10.1016/j.ymgme.2017.10.012

Abstract

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.

Keywords: Biomarkers; Carrier testing; Diagnosis; Lysophosphatidylcholine; Newborn screening; Peroxisome.

Publication types

Comparative Study

MeSH terms

ATP Binding Cassette Transporter, Subfamily D, Member 1 / genetics
Adrenoleukodystrophy / complications
Adrenoleukodystrophy / diagnosis*
Adrenoleukodystrophy / physiopathology
Adult
Biomarkers / blood
Carnitine / analysis*
Case-Control Studies
Cohort Studies
Dried Blood Spot Testing / methods*
Fatty Acids / blood*
Fatty Acids / chemistry
Fatty Acids / metabolism
Female
Humans
Infant, Newborn
Lysophosphatidylcholines / analysis*
Male
Neonatal Screening / methods*
Netherlands
New York
Sensitivity and Specificity

Substances

ABCD1 protein, human
ATP Binding Cassette Transporter, Subfamily D, Member 1
Biomarkers
Fatty Acids
Lysophosphatidylcholines
Carnitine