Sensitivity of electrospray-tandem mass spectrometry using the phenylalanine/tyrosine-ratio for differential diagnosis of hyperphenylalaninemia in neonates

Schulze, Andreas; Kohlmueller, Dirk; Mayatepek, Ertan

doi:10.1016/s0009-8981(99)00016-9

Cited by 60 publications

(35 citation statements)

References 2 publications

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“…Generally, quantitative analysis requires an amino acid analysis by HPLC. Nevertheless, identification of PKU by use of the phenylalanine/tyrosine (Phe/Tyr) ratio may be more important than a precise measurement of phenylalanine for the diagnosis and characterization of PKU (8,51,52 ).…”

Section: Essential Ms/msmentioning

confidence: 99%

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Chace¹,

Kalas²,

Naylor³

2003

Clinical Chemistry

566

366

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Background: Over the past decade laboratories that test for metabolic disorders have introduced tandem mass spectrometry (MS/MS), which is more sensitive, specific, reliable, and comprehensive than traditional assays, into their newborn-screening programs. MS/MS is rapidly replacing these one-analysis, one-metabolite, one-disease classic screening techniques with a oneanalysis, many-metabolites, many-diseases approach that also facilitates the ability to add new disorders to existing newborn-screening panels. Methods: During the past few years experts have authored many valuable articles describing various approaches to newborn metabolic screening by MS/MS. We attempted to document key developments in the introduction and validation of MS/MS screening for metabolic disorders. Our approach used the perspective of the metabolite and which diseases may be present from its detection rather than a more traditional approach of describing a disease and noting which metabolites are increased when it is present. Content: This review cites important historical developments in the introduction and validation of MS/MS screening for metabolic disorders. It also offers a basic technical understanding of MS/MS as it is applied to multianalyte metabolic screening and explains why MS/MS is well suited for analysis of amino acids and acylcarnitines in dried filter-paper blood specimens. It also describes amino acids and acylcarnitines as they are detected and measured by MS/MS and their significance to the identification of specific amino acid, fatty acid, and organic acid disorders. Conclusions: Multianalyte technologies such as MS/MS are suitable for newborn screening and other mass

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Section: Essential Ms/msmentioning

confidence: 99%

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Chace¹,

Kalas²,

Naylor³

2003

Clinical Chemistry

566

366

View full text Add to dashboard Cite

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“…Acylcarnitines in dried blood spots obtained for neonatal screening were analysed on a triple quadrupole tandem mass spectrometer with an ion spray source (API 365, PE Sciex, Canada) as previously described (Rashed et al 1995;Schulze et al 1999). The individual compounds were detected by searching for the precursor ions of m/z=85, quantified by using the signal intensity ratio to the closest internal standard, and related to concentrations by using the slope derived from standard curves.…”

Section: Acylcarnitinesmentioning

confidence: 99%

Molecular and functional characterisation of mild MCAD deficiency

et al. 2001

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Molecular and functional characterisation of mild MCAD deficiencyZschocke, J.; Schulze, A.; Lindner, M.; Fiesel, S.; Olgemöller, K.; Hoffmann, G.F.; Penzien, J.; Ruiter, J.P.N.; Wanders, R.J.A.; Mayatepek, E. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 08 May 2018Abstract We report a novel mild variant of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) diagnosed in four infants who, in neonatal screening, showed abnormal acylcarnitine profiles indicative of MCADD. Three patients showed completely normal urinary organic acids and phenylpropionic acid loading tests were normal in all four patients. Enzyme studies showed residual MCAD activities between "classical" MCADD and heterozygotes. ACADM gene analysis revealed compound heterozygosity for the common mutation K329E and a novel mutation, Y67H, in two cases, and homozygosity for mutation G267R and the novel mutation S245L, respectively, in two children of consanguineous parents. As in other metabolic disorders, the distinction between "normal" and "disease" in MCAD deficiency is blurring into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.

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“…Determination of acylcarnitines by means of tandem mass spectrometry (MS/MS) is of increasing importance in the screening for disorders of inborn errors of metabolism (1)(2)(3). Metabolic screening is also applied to preterm infants, although normal ranges are not yet established.…”

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confidence: 99%

Acylcarnitine Profiles of Preterm Infants Over the First Four Weeks of Life

et al. 2002

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Measurement of free carnitine and acylcarnitines allows the detection of several inborn errors of metabolism in neonatal screening. Because available data for premature infants is limited, we studied longitudinal changes in acylcarnitine profiles of full-term and preterm neonates over the first 4 weeks of life. One hundred twenty infants were divided into four groups of 30: A, gestational age 22 to 27 wk; B, 28 to 31 wk; C, 32 to 36 wk; and D, 37 to 41 wk. Blood samples spotted on a Guthrie card were taken on days 5 and 28. Additional specimens (groups A and B only) were collected on days 1, 3, 7, and 14. Carnitine and its acyl esters were detected by looking for the precursor ions of m/z ϭ 85 using a PE Sciex API 365 electrospray ionization tandem mass spectrometer. Concentrations of free carnitine and most acylcarnitines were significantly higher in group A compared with group D postnatally. Groups B and C displayed intermediate values. Carnitine levels in infants from group A and B decreased steadily from day 1 to day 7, and recovered up to day 14 in group B only. On day 28 carnitine concentrations had further decreased in group A, while reaching postnatal levels again in group B. Postnatal carnitine levels are higher in very immature preterm infants compared with full-term infants, but become lower on day 28. However, the commonly used metabolite ratios should still allow the detection of inborn errors of metabolism. Determination of acylcarnitines by means of tandem mass spectrometry (MS/MS) is of increasing importance in the screening for disorders of inborn errors of metabolism (1-3). Metabolic screening is also applied to preterm infants, although normal ranges are not yet established. However, carnitine levels in cord blood measured by MS/MS differed between term and preterm infants (4). Another study reported increased postnatal plasma and RBC carnitine levels in preterm infants (5). No sufficient data about dried blood spot acylcarnitine profiles in premature neonates are available so far. Especially in very immature preterm infants, initiation of enteral feeding is often delayed, and total or partial parenteral nutrition is needed for a considerable period of time. Several studies have shown that carnitine levels decrease with total parenteral nutrition in term (6) as well as in preterm infants (7). Therefore, screening for inborn errors of metabolism of preterm infants, e.g. in Germany, is repeated after 2-4 wk, when oral feeding is well established (8). In this study, we investigated carnitine levels longitudinally in premature neonates by means of MS/ MS, including very immature infants (gestational age from 22 wk) during the first 4 weeks of postnatal life to test the need of individual normal ranges for metabolic screening. METHODSSolvents, reagents and internal standards. High-purity grade methanol was obtained from Merck (Darmstadt, Germany). Butanolic HCl (3 M) was prepared from high purity butanol (Merck) and HCl-gas. Stable isotopes used as internal standards were obtained from Neo Gen Scre...

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Sensitivity of electrospray-tandem mass spectrometry using the phenylalanine/tyrosine-ratio for differential diagnosis of hyperphenylalaninemia in neonates

Cited by 60 publications

References 2 publications

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Molecular and functional characterisation of mild MCAD deficiency

Acylcarnitine Profiles of Preterm Infants Over the First Four Weeks of Life

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