Adrenoleukodystrophy Newborn Screening in the Netherlands (SCAN Study): The X-Factor

Barendsen, Rinse W.; Dijkstra, Inge M. E.; Visser, W. J.; Alders, Mariëlle; Bliek, Jet; Boelen, Anita; Bouva, Marelle J.; Crabben, Saskia N. van der; Elsinghorst, Ellen; Gorp, Ankie G. M. van; Heijboer, Annemieke C.; Jansen, M.C.J.F.; Jaspers, Yorrick R. J.; Lenthe, Henk van; Metgod, Ingrid; Mooij, Christiaan F.; Sluijs, Elise H. C. van der; Trotsenburg, A S Paul van; Verschoof-Puite, Rendelien K; Vaz, Frédéric M.; Waterham, Hans R.; Wijburg, Frits A.; Engelen, Marc; Dekkers, Eugènie; Kemp, Stephan

doi:10.3389/fcell.2020.00499

Cited by 48 publications

(66 citation statements)

References 41 publications

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“…Most laboratories use commercial kits that screen for a predefined mutation panel covering the more prevalent pathogenic variants. In recent years, many pilot projects have introduced DNA analysis into NBS before the family is alerted [ 85 , 86 , 87 , 88 ]. A retrospective study conducted in Pennsylvania evaluated the feasibility of a DNA-based 2-TT, covering the most common GALT mutations (seven mutations and two variants), to improve the specificity of NBS for Galactosemia.…”

Section: Molecular Testing As a 2-ttmentioning

confidence: 99%

Development of Strategies to Decrease False Positive Results in Newborn Screening

Malvagia

Forni

Ombrone

et al. 2020

IJNS

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The expansion of national newborn screening (NBS) programmes has provided significant benefits in the diagnosis and early treatment of several rare, heritable conditions, preventing adverse health outcomes for most affected infants. New technological developments have enabled the implementation of testing panel covering over 50 disorders. Consequently, the increment of false positive rate has led to a high number of healthy infants recalled for expensive and often invasive additional testing, opening a debate about the harm-benefit ratio of the expanded newborn screening. The false-positive rate represents a challenge for healthcare providers working in NBS systems. Here, we give an overview on the most commonly used strategies for decreasing the adverse effects due to inconclusive screening results. The focus is on NBS performance improvement through the implementation of analytical methods, the application of new and more informative biomarkers, and by using post-analytical interpretive tools. These strategies, used as part of the NBS process, can to enhance the positive predictive value of the test and reduce the parental anxiety and healthcare costs related to the unnecessary tests and procedures.

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Section: Molecular Testing As a 2-ttmentioning

confidence: 99%

Development of Strategies to Decrease False Positive Results in Newborn Screening

Malvagia

Forni

Ombrone

et al. 2020

IJNS

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“…Importantly, its analysis is considerably faster when compared to VLCFA analysis (Hubbard et al, 2009;Huffnagel et al, 2017;Klouwer et al, 2017). In fact, the identification of C26:0-LPC as a specific and sensitive biomarker in bloodspots was of paramount importance for the initiation of ALD newborn screening (Turgeon et al, 2015;Moser et al, 2016;Barendsen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Diagnostic Performance of C26:0-Lysophosphatidylcholine and Very Long-Chain Fatty Acids Analysis for Peroxisomal Disorders

Jaspers

Ferdinandusse

Dijkstra

et al. 2020

Front. Cell Dev. Biol.

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Peroxisomes are subcellular organelles that are involved in various important physiological processes such as the oxidation of fatty acids and the biosynthesis of bile acids and plasmalogens. The gold standard in the diagnostic work-up for patients with peroxisomal disorders is the analysis of very long-chain fatty acid (VLCFA) levels in plasma. Alternatively, C26:0-lysophosphatidylcholine (C26:0-LPC) can be measured in dried blood spots (DBS) using liquid chromatography tandem mass spectrometry (LC-MS/MS); a fast and easy method but not yet widely used. Currently, little is known about the correlation of C26:0-LPC in DBS and C26:0-LPC in plasma, and how C26:0-LPC analysis compares to VLCFA analysis in diagnostic performance. We investigated the correlation between C26:0-LPC levels measured in DBS and plasma prepared from the same blood sample. For this analysis we included 43 controls and 38 adrenoleukodystrophy (ALD) (21 males and 17 females) and 33 Zellweger spectrum disorder (ZSD) patients. In combined control and patient samples there was a strong positive correlation between DBS C26:0-LPC and plasma C26:0-LPC, with a Spearman's rank correlation coefficient of r (114) = 0.962, p < 0.001. These data show that both plasma and DBS are suitable to determine blood C26:0-LPC levels and that there is a strong correlation between C26:0-LPC levels in both matrices. Following this, we investigated how VLCFA and C26:0-LPC analysis compare in diagnostic performance for 67 controls, 26 ALD males, 19 ALD females, and 35 ZSD patients. For C26:0-LPC, all ALD and ZSD samples had C26:0-LPC levels above the upper limit of the reference range. For C26:0, one out of 67 controls had C26:0 levels above the upper reference range. For 1 out of 26 (1/26) ALD males, 1/19 ALD females and 3/35 ZSD patients, the C26:0

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“…As newborn screening for ALD has recently been implemented, there is an urgent need for identification of markers which may be prognostic of cerebral demyelination in many newly diagnosed patients around the world (Moser et al, 2016;Barendsen et al, 2020). Our research focuses on delineating the enormous phenotypic variability in ALD, with the overarching goal of identifying biomarkers prognostic of the advancement to CALD.…”

Section: Introductionmentioning

confidence: 99%

Multi-Omic Approach to Identify Phenotypic Modifiers Underlying Cerebral Demyelination in X-Linked Adrenoleukodystrophy

Richmond

Kloet

Vaz

et al. 2020

Front. Cell Dev. Biol.

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X-linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, and is characterized by the accumulation of very long-chain fatty acids in plasma and tissues. Disease-causing mutations are 'loss of function' mutations, with no prognostic value with respect to the clinical outcome of an individual. All male patients with ALD develop spinal cord disease and a peripheral neuropathy in adulthood, although age of onset is highly variable. However, the lifetime prevalence to develop progressive white matter lesions, termed cerebral ALD (CALD), is only about 60%. Early identification of transition to CALD is critical since it can be halted by allogeneic hematopoietic stem cell therapy only in an early stage. The primary goal of this study is to identify molecular markers which may be prognostic of cerebral demyelination from a simple blood sample, with the hope that blood-based assays can replace the current protocols for diagnosis. We collected six well-characterized brother pairs affected by ALD and discordant for the presence of CALD and performed multi-omic profiling of blood samples including genome, epigenome, transcriptome, metabolome/lipidome, and proteome profiling. In our analysis we identify discordant genomic alleles present across all families as well as differentially abundant molecular features across the omics technologies. The analysis was focused on univariate modeling to discriminate the two phenotypic groups, but was unable to identify statistically significant candidate molecular markers. Our study

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Adrenoleukodystrophy Newborn Screening in the Netherlands (SCAN Study): The X-Factor

Cited by 48 publications

References 41 publications

Development of Strategies to Decrease False Positive Results in Newborn Screening

Development of Strategies to Decrease False Positive Results in Newborn Screening

Comparison of the Diagnostic Performance of C26:0-Lysophosphatidylcholine and Very Long-Chain Fatty Acids Analysis for Peroxisomal Disorders

Multi-Omic Approach to Identify Phenotypic Modifiers Underlying Cerebral Demyelination in X-Linked Adrenoleukodystrophy

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