Newborn screening for inherited metabolic diseases using tandem mass spectrometry in China: Outcome and cost–utility analysis

Objectives Few studies in China have focused on the economic evaluation of newborn screening (NBS) for inherited metabolic disorders (IMDs) by tandem mass spectrometry (MS/MS). This study assesses the total costs, benefits, benefit–cost ratio (BCR), cost–utility ratio (CUR) and incremental cost–utility ratio (ICUR) of NBS using MS/MS compared to the non-screened group. Methods The NBS outcomes of newborns who underwent MS/MS screening for IMDs in 2009–2018 were retrospectively reviewed. Records were extracted from a screening management system at the NBS Center of Zhejiang province. A cost–benefit analysis of screening was conducted, assessing screening costs for each subject, and direct and indirect treatment costs for IMDs detected by screening. The putative benefit of clinical outcomes related to early diagnosis was assumed to be improvement in quality of life and prolonged life expectancy in the screened group, as compared to the non-screened group. Results Of the 3,040,815 newborns screened, 735 (2.86%) cases were diagnosed through gene sequence analysis. The most frequently occurring types of IMD were amino acid disorders ( n = 276), then fatty acid oxidation disorders ( n = 248), followed by organic acidaemias ( n = 211). The difference in quality-adjusted life-years (QALYs) ranged from 0.78 to 15.4 in the screened group. The CUR was CNY¥ 116,183.89/QALY in the screened group and CNY¥ 3,078,823.65/QALY in the non-screened group. The ICUR was CNY¥ –768,428.76/QALY, and the BCR was 6.09. Conclusions NBS using MS/MS can be considered cost-effective in China. The nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity.

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Newborn Screening for Inherited Metabolic Diseases Using Tandem Mass Spectrometry in China: outcome and cost-utility analysis

10.21203/rs.3.rs-124404/v1 ◽

2020 ◽

Author(s):

Zixuan Zhao ◽

Chi Chen ◽

Xueshan Sun ◽

Duo ZHOU ◽

Xinwen Huang ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Metabolic Diseases ◽

Life Time ◽

Cost Utility ◽

Acid Oxidation ◽

Cost Ratio ◽

Tandem Mass ◽

Inherited Metabolic Diseases

Abstract BackgroundFew studies in China have focused on economic evaluation of newborn screening(NBS) for inherited metabolic diseases (IMDs) by tandem mass spectrometry (MS/MS). This study assessed the total costs, benefits, benefit-cost ratio(BCR), cost-utility ratio(CUR) and incremental cost-utility ratio(ICUR) of NBS using MS/MS compared to non-screening group for the first time.MethodsThis study was conducted as a retrospective piece. Newborns who underwent MS/MS screening for IMDs from 2009 to 2018 were included. All records were extracted from a screening management system in NBS Center of Zhejiang province. All costs, including indirect cost, were discounted at a rate of 5% for the whole life-time. The putative benefit of clinical outcomes related to early-diagnosis through screening was assumed as improvements in quality of life and potential life expectancy in screening group.ResultsOf the 3,040,815 newborns screened, 26,297(0.86%) newborns were suspected positive after first-round screening and called back to take another MS/MS screening. 25,670(97.62%) of them followed the latter procedures and finally 735(2.86%) cases were diagnosed through gene sequence analysis. The most frequent cause of IMD was amino acid diseases(n=276), in most cases fatty acid oxidation disorders (n=248), followed by organic acidemias (n=211). The difference of QALYs ranged from 0.78-15.4. The CUR was CNY¥86,155.80/QALY in screening group and CNY¥303,9517.32/QALY in non-screening group. The ICUR was CNY¥-795,686.47/QALY, and the BCR was 1:8.11.ConclusionsNBS using MS/MS can be considered as cost-effective. Nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity.

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The role of tandem mass spectrometry in the diagnosis of inherited metabolic diseases

Russian Journal of Pediatric Hematology and Oncology ◽

10.17650/2311-1267-2018-5-3-96-105 ◽

2018 ◽

Vol 5 (3) ◽

pp. 96-105 ◽

Cited By ~ 2

Author(s):

G. V. Baydakova ◽

T. A. Ivanova ◽

E. Yu. Zakharova ◽

O. S. Kokorina

Keyword(s):

Mass Spectrometry ◽

Fatty Acid ◽

Tandem Mass Spectrometry ◽

Fatty Acid Oxidation ◽

Metabolic Diseases ◽

Acid Oxidation ◽

Tandem Mass ◽

Organic Acidurias ◽

Inherited Metabolic Diseases ◽

Screening Programs

This paper reviews the clinical applications of tandem mass spectrometry in diagnosis and screening for inherited metabolic diseases. The broad-spectrum of diseases covered, specificity, ease of sample preparation, and high throughput provided by the MS/MS technology has led to the development of multi-disorder newborn screening programs in many countries for amino acid disorders, organic acidurias, and fatty acid oxidation defects. The application of MS/MS in selective screening has revolutionized the field and made a major impact on the detection of certain disease classes such as the fatty acid oxidation defects. New specific and rapid tandem mass spectrometry (MS/MS) and high performance liquid chromatography–MS/MS methods are supplementing or replacing some of the classical gas chromatography– MS/MS methods for a multitude of metabolites and disorders. In the near future, we should expect the emergence of new promising methods for diagnosing not only individual nosologic forms, but also entire groups of inherited metabolic diseases.

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PIH24 COST-UTILITY ANALYSIS OF NEWBORN SCREENING PROGRAM BY TANDEM MASS SPECTROMETRY IN JAPAN

Value in Health ◽

10.1016/j.jval.2019.09.1205 ◽

2019 ◽

Vol 22 ◽

pp. S632

Author(s):

K. Konomura ◽

Y. Tamura ◽

M. Akazawa ◽

T. Fukuda

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Screening Program ◽

Cost Utility ◽

Cost Utility Analysis ◽

Tandem Mass ◽

Newborn Screening Program ◽

Utility Analysis

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Disorders of Fatty Acid Oxidation in the Era of Tandem Mass Spectrometry in Newborn Screening

Newborn and Infant Nursing Reviews ◽

10.1053/j.nainr.2007.12.014 ◽

2008 ◽

Vol 8 (1) ◽

pp. 18-29 ◽

Cited By ~ 1

Author(s):

Sandra A. Banta-Wright ◽

Kathleen C. Shelton ◽

Michael J. Bennett

Keyword(s):

Mass Spectrometry ◽

Fatty Acid ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Tandem Mass

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Tryptic Peptide Analysis of Ceruloplasmin in Dried Blood Spots Using Liquid Chromatography–Tandem Mass Spectrometry: Application to Newborn Screening

Clinical Chemistry ◽

10.1373/clinchem.2008.111989 ◽

2008 ◽

Vol 54 (12) ◽

pp. 1961-1968 ◽

Cited By ~ 69

Author(s):

Amy deWilde ◽

Katerina Sadilkova ◽

Martin Sadilek ◽

Valeria Vasta ◽

Si Houn Hahn

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Wilson Disease ◽

Metabolic Diseases ◽

Screening Methods ◽

Tandem Mass ◽

Limit Of Quantification ◽

Large Proteins

Abstract Background: Newborn screening to identify infants with treatable congenital disorders is carried out worldwide. Recent tandem mass spectrometry (MS/MS) applications have markedly expanded the ability to screen for >50 metabolic diseases with a single dried blood spot (DBS). The feature that makes metabolic disorders particularly amenable to screening is the presence of specific small-molecule metabolites. Many treatable disorders such as Wilson disease, however, are characterized by absent or diminished large proteins in plasma or within circulating blood cells, for which there are currently no cost-effective screening methods. Methods: We developed an assay for quantifying ceruloplasmin (CP) in DBS for newborn screening of Wilson disease. CP-specific peptides from DBS samples digested by trypsin were quantified using isotopically labeled peptide internal standards and liquid chromatography–triple quadrupole mass spectrometry (LC-MS/MS). Results: The calibration curve was linear from 20 to 95 mg/dL (200–950 mg/L). Intraassay imprecision (mean CV) for CP concentrations of 25, 35, and 55 mg/dL (250, 350, and 550 mg/L) was 9.2%, 10.7%, and 10.2%, respectively. Interassay imprecision for 19 different batches was 8.9%, 5.8%, and 6.9%. A method comparison study on previously tested patient samples for CP gave comparable results with lower limit of quantification, around 0.7 mg/dL (7 mg/L). Conclusions: Our study supports that newborn screening for Wilson disease is feasible using LC-MS/MS assay for CP quantification in DBS after tryptic digestion. This approach should be applicable to newborn screening for other treatable genetic conditions, such as primary immunodeficiencies, that have large proteins as biomarkers.

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Cost-Benefit Analysis of Universal Tandem Mass Spectrometry for Newborn Screening

PEDIATRICS ◽

10.1542/peds.110.4.781 ◽

2002 ◽

Vol 110 (4) ◽

pp. 781-786 ◽

Cited By ~ 67

Author(s):

E. J. Schoen ◽

J. C. Baker ◽

C. J. Colby ◽

T. T. To

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Cost Benefit Analysis ◽

Cost Benefit ◽

Tandem Mass ◽

Benefit Analysis

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Newborn screening and molecular features of patients with multiple acyl-CoA dehydrogenase deficiency in Quanzhou, China

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0694 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Yiming Lin ◽

Weifeng Zhang ◽

Zhixu Chen ◽

Chunmei Lin ◽

Weihua Lin ◽

...

Keyword(s):

Mass Spectrometry ◽

Genetic Analysis ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Dehydrogenase Deficiency ◽

Late Onset ◽

False Negative ◽

Tandem Mass ◽

Lipid Storage Myopathy ◽

Molecular Features

Abstract Objectives Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid and choline metabolism. Late-onset MADD is caused by ETFDH mutations and is the most common lipid storage myopathy in China. However, few patients with MADD have been identified through newborn screening (NBS). This study assessed the acylcarnitine profiles and molecular features of patients with MADD identified through NBS. Methods From January 2014 to June 2020, 479,786 newborns screened via tandem mass spectrometry were recruited for this study. Newborns with elevated levels of multiple acylcarnitines were recalled, those who tested positive in the reassessment were referred for genetic analysis. Results Of 479,786 newborns screened, six were diagnosed with MADD. The MADD incidence in the Chinese population was estimated to be 1:79,964. Initial NBS revealed five patients with typical elevations in the levels of multiple acylcarnitines; however, in one patient, acylcarnitine levels were in the normal reference range during recall. Notably, one patient only exhibited a mildly increased isovalerylcarnitine (C5) level at NBS. The patient with an atypical acylcarnitine profile was diagnosed with MADD by targeted gene sequencing. Six distinct ETFDH missense variants were identified, with the most common variant being c.250G>A (p.A84T), with an allelic frequency of 58.35 (7/12). Conclusions These findings revealed that it is easy for patients with MADD to go unidentified, as they may have atypical acylcarnitine profiles at NBS and the recall stage, indicating the value of genetic analysis for confirming suspected inherited metabolic disorders in the NBS program. Therefore, false-negative (FN) results may be reduced by combining tandem mass spectrometry (MS/MS) with genetic testing in NBS for MADD.

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