Simultaneous quantitation of hexacosanoyl lysophosphatidylcholine, amino acids, acylcarnitines, and succinylacetone during FIA–ESI–MS/MS analysis of dried blood spot extracts for newborn screening

Haynes, Christopher A.; Jesús, Víctor R. De

doi:10.1016/j.clinbiochem.2015.09.011

Cited by 26 publications

(18 citation statements)

References 16 publications

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“…The procedure has been slightly modified [ 14 , 15 ] to combine the existing method for acylcarnitine analysis and C26:0-lysoPC, which enables simultaneous extraction and screening for peroxisomal disorders, mitochondrial fatty acid oxidation disorders and organic acidurias. Recently, a method was developed that enables the quantification of amino acids, acylcarnitines, succinylacetone, and C26:0-lysoPC in a single dried bloodspot punch [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 99%

C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man

et al. 2016

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“…Earlier studies determined plasma VLCFAs as their methyl esters followed by detection using GC or GC-MS assays [5] , [6] . Subsequently, among many species of VLCFAs, 1-hexacosanoyl-2-hydroxy- sn -glycero-3-phosphocholine (Lyso-PC 26:0) has been proposed as a sensitive biomarker for X-ALD [7] , [8] , [9] , [10] . The milestone study demonstrated that an increasing Lyso-PC 26:0 levels in the dried blood spots (DBSs) from X-ALD patients using liquid chromatography with mass spectrometric detection (LC-MS/MS) [7] .…”

Section: Introductionmentioning

confidence: 99%

A selective detection of lysophosphatidylcholine in dried blood spots for diagnosis of adrenoleukodystrophy by LC-MS/MS

Mashima

Tanaka

Sakai

et al. 2016

Molecular Genetics and Metabolism Reports

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X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disorder characterized by an impaired beta-oxidation of very long chain fatty acids in the peroxisomes. Recent studies have suggested that 1-hexacosanoyl-2-hydroxy-sn-glycero-3-phosphocholine (Lyso-PC 26:0) can be a sensitive biomarker for X-ALD. Although approximately 10-fold increase in the concentration of Lyso-PC 26:0 in DBSs from X-ALD-affected individuals were reported, whether the carriers might be distinguished from the healthy controls remained unclear. To address this question, we have validated previously developed LC-MS/MS-based analytical procedures using QC DBS. We found that the recovery of Lyso-PC 26:0 from the QC DBSs was 73.6 ± 0.3% when 2 μM of Lyso-PC 26:0 was spiked into the blood. Based on this result, the amounts of Lyso-PC 26:0 in the controls and ALD-affected individuals were 0.090 ± 0.004 (n = 11) and 1.078 ± 0.217 (n = 4) pmol/DBS, respectively. Interestingly, the concentration of Lyso-PC 26:0 in the carriers were 0.548 ± 0.095 pmol/DBS (n = 3), indicating that the carriers and the healthy controls can be distinguished. These results suggest that LC-MS/MS-based technique can be used for the detection of asymptomatic carriers and X-ALD-affected subjects in the newborn screening.

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“…A high-throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been established to measure C26:0-lysoPC in DBS (Hubbard et al 2009) and this method has already been implemented in newborn screening programs for ALD in some countries (Vogel et al 2015). In studies on C26:0-lysoPC levels in ALD patients a limited number of ZSD patients with elevated C26:0-lysoPC levels have also been identified (Hubbard et al 2006;Haynes and De Jesús 2016), but no specific studies on C26:0-lysoPC accumulation in ZSD patients have been performed. Also, little is known about the sensitivity and specificity of this biomarker for ZSD.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of C26:0‐lysophosphatidylcholine and C26:0‐carnitine as diagnostic markers for Zellweger spectrum disorders

Klouwer

Ferdinandusse

Lenthe

et al. 2017

J of Inher Metab Disea

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Introduction Zellweger spectrum disorders (ZSD) are a group of genetic metabolic disorders caused by a defect in peroxisome biogenesis. This results in multiple metabolic abnormalities, including elevated very long-chain fatty acid (VLCFA) levels. Elevated levels of C26:0-lysophosphatidylcholine (C26:0-lysoPC) have been shown in dried blood spots (DBS) from ZSD patients. However, little is known about the sensitivity and specificity of this marker and C26:0-carnitine, another VLCFA-marker, in ZSD. We investigated C26:0-lysoPC and C26:0-carnitine as diagnostic markers for ZSD in DBS and fibroblasts. Methods C26:0-lysoPC levels in 91 DBS from 37 different ZSD patients were determined and compared to the levels in 209 control DBS. C26:0-carnitine levels were measured in 41 DBS from 29 ZSD patients and 97 control DBS. We measured C26:0-lysoPC levels in fibroblasts from 24 ZSD patients and 61 control individuals. Results Elevated C26:0-lysoPC levels (>72 nmol/L) were found in 86/91 ZSD DBS (n=33/37 patients) corresponding to a sensitivity of 89.2%. Median level was 567 nmol/l (range 28-3133 nmol/l). Consistently elevated C26:0-carnitine levels (>0.077 μmol/L) in DBS were found in 16 out of 29 ZSD patients corresponding to a sensitivity of 55.2%. C26:0-lysoPC levels were elevated in 21/24 ZSD fibroblast lines. Discussion C26:0-lysoPC in DBS is a sensitive and useful marker for VLCFA accumulation in patients with a ZSD. C26:0-carnitine in DBS is elevated in some ZSD patients, but is less useful as a diagnostic marker. Implementation of C26:0-lysoPC measurement in the diagnostic work-up when suspecting a ZSD is advised. This marker has the potential to be used for newborn screening for ZSD.

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Simultaneous quantitation of hexacosanoyl lysophosphatidylcholine, amino acids, acylcarnitines, and succinylacetone during FIA–ESI–MS/MS analysis of dried blood spot extracts for newborn screening

Cited by 26 publications

References 16 publications

C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man

C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man

A selective detection of lysophosphatidylcholine in dried blood spots for diagnosis of adrenoleukodystrophy by LC-MS/MS

Evaluation of C26:0‐lysophosphatidylcholine and C26:0‐carnitine as diagnostic markers for Zellweger spectrum disorders

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