scholarly journals Newborn Screening for X-Linked Adrenoleukodystrophy in Georgia: Experiences from a Pilot Study Screening of 51,081 Newborns

2020 ◽  
Vol 6 (4) ◽  
pp. 81
Author(s):  
Patricia L. Hall ◽  
Hong Li ◽  
Arthur F. Hagar ◽  
S. Caleb Jerris ◽  
Angela Wittenauer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pilot Study ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Clinical Findings ◽  
Molecular Testing ◽  
Tandem Mass ◽  
Test Results ◽  
Second Tier

We screened 51,081 newborns for X-linked adrenoleukodystrophy (ALD) using a two-tiered strategy quantifying very long chain lysophosphatadylcholines (LPC). Our testing strategy used flow injection tandem mass spectrometry for the first-tier analysis of LPCs, and second-tier quantification of C26:0 LPC using liquid chromatography tandem mass spectrometry. There were 364 specimens considered abnormal using our first-tier algorithm that relied on the four LPC measurements and post-analytical tools. Second-tier test results were reported as normal or abnormal based on a cutoff for the single analyte, C26:0 LPC. Eleven cases were reported as abnormal based on second-tier test results. One male with ALD was identified, and two females with peroxisomal biogenesis disorders were also identified. A single female case remains unresolved, due to a loss to follow up after a negative molecular test result for ABCD1 gene sequencing. The positive predictive value for confirmed, clinically relevant disorders during this pilot study was 27.3%. Challenges identified during the study period were based around coverage for confirmatory testing, particularly if family members needed molecular testing, which is an ongoing issue with newborn screening in Georgia. We also encountered issues with the follow up for a patient who remained asymptomatic. Due to the different timelines involved with clinical findings in ALD, follow-up coordination may be more difficult, particularly if the child identified by newborn screening (NBS) is the only member of the family affected, or able to be tested.

scholarly journals National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Follow-Up Testing for Metabolic Disease Identified by Expanded Newborn Screening Using Tandem Mass Spectrometry; Executive Summary

2009 ◽  
Vol 55 (9) ◽  
pp. 1615-1626 ◽  
Author(s):  
Dennis J Dietzen ◽  
Piero Rinaldo ◽  
Ronald J Whitley ◽  
William J Rhead ◽  
W Harry Hannon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Tandem Mass Spectrometry ◽  
Organic Acids ◽  
Newborn Screening ◽  
Tandem Mass ◽  
Confirmatory Testing ◽  
The Us ◽  
The Impact

Abstract Background: Almost all newborns in the US are screened at birth for multiple inborn errors of metabolism using tandem mass spectrometry. Screening tests are designed to be sufficiently sensitive so that cases are not missed. The NACB recognized a need for standard guidelines for laboratory confirmation of a positive newborn screen such that all babies would benefit from equal and optimal follow-up by confirmatory testing. Methods: A committee was formed to review available data pertaining to confirmatory testing. The committee evaluated previously published guidelines, published methodological and clinical studies, clinical case reports, and expert opinion to support optimal confirmatory testing. Grading was based on guidelines adopted from criteria derived from the US Preventive Services Task Force and on the strength of recommendations and the quality of the evidence. Three primary methods of analyte measurement were evaluated for confirmatory testing including measurement of amino acids, organic acids, and carnitine esters. The committee graded the evidence for diagnostic utility of each test for the screened conditions. Results: Ample data and experience were available to make strong recommendations for the practice of analyzing amino acids, organic acids, and acylcarnitines. Likewise, strong recommendations were made for the follow-up test menu for many disorders, particularly those with highest prevalence. Fewer data exist to determine the impact of newborn screening on patient outcomes in all but a few disorders. The guidelines also provide an assessment of developing technology that will fuel a refinement of current practice and ultimate expansion of the diseases detectable by tandem mass spectrometry. Conclusions: Guidelines are provided for optimal follow-up testing for positive newborn screens using tandem mass spectrometry. The committee regards these tests as reliable and currently optimal for follow-up testing. .

scholarly journals Performance of the Four-Plex Tandem Mass Spectrometry Lysosomal Storage Disease Newborn Screening Test: The Necessity of Adding a 2nd Tier Test for Pompe Disease

2018 ◽  
Vol 4 (4) ◽  
pp. 41 ◽  
Author(s):  
Shu-Chuan Chiang ◽  
Pin-Wen Chen ◽  
Wuh-Liang Hwu ◽  
An-Ju Lee ◽  
Li-Chu Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Screening Test ◽  
Disease Screening ◽  
Confirmatory Test ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Second Tier

Early diagnosis of lysosomal storage diseases (LSDs) through newborn screening (NBS) has been adapted widely. The National Taiwan University Hospital Newborn Screening Center launched the four-plex tandem mass spectrometry LSD newborn screening test in 2015. The test determined activities of acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), acid β-glucocerebrosidase (ABG; Gaucher), and acid α-l-iduronidase (IDUA; MPS-I) in dried blood spots (DBS). Through 2017, 64,148 newborns were screened for these four LSDs. The screening algorithm includes enzyme activity/ratio as the cutoffs for the first screening test and a second-tier test for Pompe disease screening. The second-tier Pompe disease screening test measured activity inhibition by acarbose. Twenty-nine newborns required a confirmatory test; six were confirmed to have Pompe disease, and nine were confirmed to have Fabry disease. The screen-positive rate for Pompe disease was 0.031%. Therefore, in Pompe disease newborn screening, a validated 2nd tier test is necessary to decrease false positives.

Determination of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots by liquid chromatography–tandem mass spectrometry: A reliable follow-up method for propionylcarnitine-related disorders in newborn screening

2020 ◽  
pp. 096914132093772
Author(s):  
Zhenzhen Hu ◽  
Jianbin Yang ◽  
Yiming Lin ◽  
Junjuan Wang ◽  
Lingwei Hu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Methylmalonic Acid ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Total Homocysteine

Objectives Determination of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots by liquid chromatography–tandem mass spectrometry has usually been used as a second-tier test to improve performance of newborn screening for propionylcarnitine-related disorders. However, factors that potentially affect its detection results have not been investigated, and we aimed to evaluate these influencing factors and explore their potential utility in newborn screening and initial follow-up for propionylcarnitine-related disorders. Methods This study comprised a prospective group (1998 healthy infants, to establish cutoff values and investigate the influencing factors) and a retrospective group (804 suspected positive cases screened from 381, 399 newborns for propionylcarnitine-related disorders by tandem mass spectrometry, to evaluate the performance of newborn screening and initial follow-up). Results Cutoff values for methylmalonic acid, 2-methylcitric acid, and total homocysteine were 2.12, 0.70, and 10.05 µmol/l, respectively. Concentration of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots is not impacted by sex, age, birth weight, gestational age, or dried blood spot storage time. A total of 75 of 804 cases were screened positive by combined tandem mass spectrometry and liquid chromatography–tandem mass spectrometry, thus eliminating 90% of the false positives without compromising sensitivity. Eighteen propionylcarnitine-related disorders were successfully identified, including one CblX case missed in the initial follow-up by tandem mass spectrometry. Conclusions Methylmalonic acid, 2-methylcitric acid, and total homocysteine detected in dried blood spots by liquid chromatography–tandem mass spectrometry is a reliable, specific, and sensitive approach for identifying propionylcarnitine-related disorders. We recommend this assay should be performed rather than tandem mass spectrometry in follow-up for propionylcarnitine-related disorders besides second-tier tests in newborn screening.

scholarly journals Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study

2016 ◽  
Vol 23 (3) ◽  
pp. 124-129 ◽  
Author(s):  
Fayza A Hassan ◽  
Fatma El-Mougy ◽  
Sahar A Sharaf ◽  
Iman Mandour ◽  
Marian F Morgan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pilot Study ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Inborn Errors Of Metabolism ◽  
Tandem Mass ◽  
Inborn Errors

scholarly journals Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

2016 ◽  
Vol 40 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Francyne Kubaski ◽  
Robert W. Mason ◽  
Akiko Nakatomi ◽  
Haruo Shintaku ◽  
Li Xie ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pilot Study ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Tandem Mass

scholarly journals Development of Second-Tier Liquid Chromatography-Tandem Mass Spectrometry Analysis for Expanded Newborn Screening in Japan

2021 ◽  
Vol 7 (3) ◽  
pp. 44
Author(s):  
Yosuke Shigematsu ◽  
Miori Yuasa ◽  
Nobuyuki Ishige ◽  
Hideki Nakajima ◽  
Go Tajima
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Organic Acids ◽  
Newborn Screening ◽  
Mass Spectrometry Analysis ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Second Tier

To minimize false-positive cases in newborn screening by tandem mass spectrometry in Japan, practical second-tier liquid chromatography-tandem mass spectrometry analyses have been developed using a multimode ODS column with a single set of mobile phases and different gradient elution programs specific to the analysis of acylcarnitines, acylglycines, amino acids, and organic acids. Most analyses were performed using underivatized samples, except for analysis of methylcitric acid, and careful conditioning of the column was necessary for analyses of organic acids. Our second-tier tests enabled us to measure many metabolites useful for detection of target disorders, including allo-isoleucine, homocysteine, methylmalonic acid, and methylcitric acid. We found that accumulation of 3-hydroxyglutaric acid was specific to glutaric acidemia type I and that the ratio of 3-hydroxyisovaleric acid to 3-hydroxyisovalerylcarnitine was useful to detect newborns of mothers with 3-methylcrotonyl-CoA carboxylase deficiency. Data from the analysis of short-chain acylcarnitine and acylglycine were useful for differential diagnosis in cases positive for C5-OH-acylcarnitine or C5-acylcarnitine.

scholarly journals Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry

2016 ◽  
Vol 118 (4) ◽  
pp. 304-309 ◽  
Author(s):  
Susan Elliott ◽  
Norman Buroker ◽  
Jason J. Cournoyer ◽  
Anna M. Potier ◽  
Joseph D. Trometer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pilot Study ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases

scholarly journals Partial Biotinidase Deficiency Revealed Imbalances in Acylcarnitines Profile at Tandem Mass Spectrometry Newborn Screening

2021 ◽  
Vol 18 (4) ◽  
pp. 1659
Author(s):  
Ilaria Cicalini ◽  
Damiana Pieragostino ◽  
Cristiano Rizzo ◽  
Sara Verrocchio ◽  
Daniela Semeraro ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Metabolic Profile ◽  
Late Onset ◽  
Normal Activity ◽  
Molecular Testing ◽  
Tandem Mass ◽  
Multiple Carboxylase Deficiency ◽  
First Time

Biotinidase (BTD) deficiency is an autosomal recessive inherited neurocutaneous disorder. BTD recycles the vitamin biotin, a coenzyme essential for the function of four biotin-dependent carboxylases, including propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and acetyl-CoA carboxylase. Due to deficient activities of the carboxylases, BTD deficiency is also recognized as late-onset multiple carboxylase deficiency and is associated with secondary alterations in the metabolism of amino acids, carbohydrates, and fatty acids. BTD deficiency can be classified as “profound”, with less than 10% of mean normal activity, and as “partial” with 10–30% of mean normal activity. Newborn screening (NBS) of BTD deficiency is performed in most countries and is able to detect both variants. Moreover, mild metabolic alterations related to carboxylase deficiency in profound BTD deficiency could result and possibly be revealed in the metabolic profile by tandem mass spectrometry (MS/MS) NBS. Here, we report the case of a newborn female infant with an initial suspected BTD deficiency at the NBS test, finally confirmed as a partial variant by molecular testing. Although BTD deficiency was partial, interestingly her metabolic profile at birth and during the follow-up tests revealed, for the first time, alterations in specific acylcarnitines as a possible result of the deficient activity of biotin-dependent carboxylases.

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