Flow injection ionization-tandem mass spectrometry-based estimation of a panel of lysophosphatidylcholines in dried blood spots for screening of X-linked adrenoleukodystrophy

Natarajan, Archana; Christopher, Rita; Netravathi, M; Bhat, Maya; Chandra, Sadanandavalli Retnaswami

doi:10.1016/j.cca.2019.04.059

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…The PerkinElmer X-ALD NBS protocol employed a two-tiered testing process to detect X-ALD and eliminate interference occurring at the same mass as C26:0-lysophosphatidylcholine (C26:0-LPC) ( Figure 1 ). The first-tier test was performed via flow injection analysis tandem mass spectrometry (FIA-MS/MS) to measure C26:0-LPC [ 35 ]. An 1/8” punched dried blood spot was extracted in methanol at room temperature with a D4-C26:0-LPC internal standard.…”

Section: Methodsmentioning

confidence: 99%

Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

Priestley

Adang

Williams

et al. 2022

IJNS

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X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.

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Section: Methodsmentioning

confidence: 99%

Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

Priestley

Adang

Williams

et al. 2022

IJNS

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“…Yet, when using lysoPC C26:0 as only marker, there is a considerable overlap between controls and X-ALD patients. Similarly, to the method in this commercial kit, a study by Natarajan et al showed that utilizing flow injection mass spectrometry (FIA-MS), lysoPC C26:0 was overestimated especially in the lower concentration range [27]. Thus, maybe leading to impaired separation of controls and patients also in this commercial kit.…”

Section: Discussionmentioning

confidence: 88%

LC-MS Based Platform Simplifies Access to Metabolomics for Peroxisomal Disorders

et al. 2021

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Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to devastating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal enzyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classical markers such as very long-chain fatty acids (VLCFA), which can be inconspicuous in milder and atypical cases. Holistic metabolomics studies revealed several potentially new biomarkers for peroxisomal disorders for advanced laboratory diagnostics including atypical cases. However, establishing these new markers is a major challenge in routine diagnostic laboratories. We therefore investigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to reproduce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes PEX1, ABCD1, and the HSD17B4 gene. Here we found various changes in sphingomyelins and lysophosphatidylcholines. In conclusion, this kit can be used to carry out extended diagnostics for peroxisomal disorders in routine laboratories, even without access to a metabolomics unit.

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“… 15 A similar‐scaled study was conducted in India population aged 1–60 years and the four LPCs levels were 0.32, 0.17, 0.29, and 0.16 µM. 5 Tian et al conducted a new born screening study for determining C20:0‐C26:0‐LPCs levels in Shanghai population, involving 3078 DBS specimens. The median values of LPCs were 0.18, 0.14, 0.37, and 0.20 µM, respectively.…”

Section: Resultsmentioning

confidence: 99%

“… 4 For example, 26:0‐LPC is known to be elevated in patients and has been applied to screen X‐linked adrenoleukodystrophy (X‐ALD) and other peroxisomal disorders in the neonates. 5 Consequently, the analysis of LPCs as biomarkers of different disease states has gained considerable interest recently.…”

Section: Introductionmentioning

confidence: 99%

“… 15 A panel of LPCs (C20:0, C22:0, C24:0, and C26:0) was also analyzed in India by Natarajan et al with a reliable and fast FIA‐MS/MS method, where they measured the concentrations and the ratios of LPC. 5 Except for Tian’s work adopting the NeoBase TM 2 Non‐derivatized MSMS kit, no further reported was published on DBS‐based assay for measuring LPCs with Chinese neonates. 16 NeoBase TM 2 kit was an upgraded version of NeoBase TM 1 and it added more metabolites including 3 amino acids, 5 acylcarnitines, 4 lysophospholipids, 2 nucleosides, and the coverage was expanded to 57 metabolites.…”

Section: Introductionmentioning

confidence: 99%

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Development, validation, and clinical application of an FIA‐MS/MS method for the quantification of lysophosphatidylcholines in dried blood spots

Yue

Liu

et al. 2021

Clinical Laboratory Analysis

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Flow injection ionization-tandem mass spectrometry-based estimation of a panel of lysophosphatidylcholines in dried blood spots for screening of X-linked adrenoleukodystrophy

Cited by 7 publications

References 32 publications

Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

LC-MS Based Platform Simplifies Access to Metabolomics for Peroxisomal Disorders

Development, validation, and clinical application of an FIA‐MS/MS method for the quantification of lysophosphatidylcholines in dried blood spots

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