Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

Marca, Giancarlo la; Malvagia, Sabrina; Pasquini, Elisabetta; Innocenti, Marzia; Donati, Maria Alice; Zammarchi, Enrico

doi:10.1373/clinchem.2007.087775

Cited by 108 publications

(97 citation statements)

References 15 publications

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“…For example, acylcarnitines are unstable if stored at room temperature for more than 2 weeks on DBS due to hydrolysis, but they are stable for at least 330 days when stored at ≤−18°C . Without establishing the analyte storage stability coverage (from sample collection to analysis), a retrospective reanalysis of the study samples might not be confi rmative for any purpose, especially for newborn screening, for which the confi rmatory analysis (secondtier test) is often conducted, but only after the initial population screening Lai et al, 2001Lai et al, , 2002la Marca et al, 2007la Marca et al, , 2008aMatern et al, 2007). Stability assessment.…”

Section: Stabilitymentioning

confidence: 99%

“…Furthermore, the possible in-source fragmentation in the case that the target analyte is a derivative of another intact biomarker molecule and natural isotope contribution might add another challenge to MS/MS (infusion or fl ow injection) only assays (Garg and Dasouki, 2006;Piraud et al, 2003). Consequently, LC-MS/MS has been increasingly explored in the confi rmatory analysis (second-tier test) of those 'diffi cult' biomarker molecules, resulting in a reduced false-positive rate (Janzen et al, 2007;Lacey et al, 2004;la Marca et al, 2007 and2008a;Matern et al, 2007;Minutti et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules

Li¹,

Tse²

2009

Biomedical Chromatography

535

428

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The collection of whole blood samples on paper, known as dried blood spot (DBS), dates back to the early 1960s in newborn screening for inherited metabolic disorders. DBS off ers a number of advantages over conventional blood collection. As a less invasive sampling method, DBS off ers simpler sample collection and storage and easier transfer, with reduced infection risk of various pathogens, and requires a smaller blood volume. To date, DBS-LC-MS/MS has emerged as an important method for quantitative analysis of small molecules. Despite the increasing popularity of DBS-LC-MS/MS, the method has its limitations in assay sensitivity due to the small sample size. Sample quality is often a concern. Systematic assessment on the potential impact of various blood sample properties on accurate quantifi cation of analyte of interest is necessary. Whereas most analytes may be stable on DBS, unstable compounds present another challenge for DBS as enzyme inhibitors cannot be conveniently mixed during sample collection. Improvements on the chemistry of DBS card are desirable. In addition to capturing many representative DBS-LS-MS/MS applications, this review highlights some important aspects of developing and validating a rugged DBS-LC-MS/MS method for quantitative analysis of small molecules along with DBS sample collection, processing and storage.

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Section: Stabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules

Li¹,

Tse²

2009

Biomedical Chromatography

535

428

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“…PA is included in the NBS core panel, to rule out a subset of C3-related metabolic disorders resulting from propionate accumulation (PA, methylmalonic aciduria (MMA), certain cobalamin (Cbl) disorders). C3 is not specific for PA and a second-tier strategies analyzing methylmalonic acid, 3-hydroxypropionic acid, and 2-methylcitric acid from the initial DBS have been developed (la Marca et al 2007;Lindner et al 2008;Matern et al 2007). Many laboratories use ratios of C3 to other acylcarnitine species (C2, C0, C16) or to methionine to improve specificity and sensitivity of C3 test (Wikoff et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Expansion of the Phenotypic Spectrum of Propionic Acidemia with Isolated Elevated Propionylcarnitine

et al. 2016

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We report three patients with elevations of propionylcarnitine (C3), one without elevations of 2-methylcitrate and 3-hydroxypropionate in urine organic acid analysis, and the other two showing only mild elevations, all of whom were subsequently confirmed to have propionic acidemia by molecular analysis of PCCA and PCCB genes. To date, they have had a mild clinical course. These cases illustrate the importance of considering high C3 as the only biochemical abnormality in a diagnosis of propionic acidemia. Since mild C3 elevations may be overlooked and considered non-diagnostic in isolation, we advise considering a diagnosis of propionic acidemia even in the absence of significant elevations 2-methylcitrate or 3-hydroxypropionate in urine organic acid analysis.Abbreviations 2-MCA 2-Methylcitrate 3-OHP 3-Hydroxypropionate C3 Propionylcarnitine

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“…In 2011 in Tuscany region, ADA SCID biomarkers were included in the panel of expanded NBS; also in this case a second tier test can be performed when elevated concentration of purines metabolites are detected [51].…”

Section: Second Tier Testsmentioning

confidence: 99%

Mass spectrometry in clinical chemistry: the case of newborn screening

Marca

2014

Journal of Pharmaceutical and Biomedical Analysis

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Keywords:Newborn screening LC-MS/MS Tandem mass spectrometry Inborn errors of metabolism Clinical chemistry a b s t r a c t Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods.Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system.

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Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

Cited by 108 publications

References 15 publications

Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules

Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules

Expansion of the Phenotypic Spectrum of Propionic Acidemia with Isolated Elevated Propionylcarnitine

Mass spectrometry in clinical chemistry: the case of newborn screening

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