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

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.

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

2021 ◽  
pp. 096914132110216
Author(s):  
Zixuan Zhao ◽  
Chi Chen ◽  
Xueshan Sun ◽  
Duo Zhou ◽  
Xinwen Huang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Metabolic Diseases ◽  
Cost Benefit Analysis ◽  
Cost Utility ◽  
Acid Oxidation ◽  
Cost Ratio ◽  
Tandem Mass ◽  
Life Years

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.

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

2018 ◽  
Vol 5 (3) ◽  
pp. 96-105 ◽  
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.

scholarly journals PRELIMINARY RESULTS ON THE USING TANDEM MASS SPECTROMETRY IN DIAGNOSIS OF INHERITED METABOLIC DISEASES

2020 ◽  
Vol 52 (01) ◽  
pp. 37-38
Author(s):  
Lyazzat Syrlybayeva
Keyword(s):  
Mass Spectrometry ◽  
Early Diagnosis ◽  
Tandem Mass Spectrometry ◽  
Death Rate ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Tandem Mass ◽  
Selective Screening ◽  
Inherited Metabolic Diseases ◽  
Blood Spot

BACKGROUND According to the results of the researches common indexes of the prevalence of inherited metabolic diseases (IMD) varies from 1 to 800 on 1 to 2500 alive newborns. IMD are taking one of the first places among children pathology, early children death (40%) and disability[1]. According to systematic review of the 43 forms of the inborn errors of metabolism are related to unexpected death of newborns. For IMD it is common to have a wide spectrum of the unusual clinical manifestation, often they are not diagnosed, while well timed diagnoses and proper treatment are able to prevent severe systematic lesions, which lead to death and disability[2]. For that reason one of the most significant problems of the modern pediatrics is to early diagnosis of IMD. The only way to diagnosis of orphan metabolic diseases is the tandem mass spectrometry (TMS) [3]. AIM Scientifically substantiate the need for implementation of selective screening IMD of children using TMS method in Republic of Kazakhstan (RK) for early diagnosis, therapy of the inherited metabolic diseases, to reduce disability and death rate. MATERIALS AND METHODS Material of the research – dry blood spots, taken using standard methodology on filtered DBS papers, which are used in RK in the program of neonatal screening (for retrospective research – archived samples of the dry blood spots of the children dead during first year of life). Method of the research is tandem mass spectometry (QSight Perkin Elmer). RESULTS Analysis of the archived dry blood spot samples showed metabolic deviations in 20.4% of the cases. The detected changes are related to amino acids metabolic disorders, defects of -oxidation of the fat acids, decrease activity of the glucocerebrosidase (Gaucher’s disease) and sphingomyelinase (Nimman – Pick disease). Results of the selective screening have shown metabolic disorders in 5% of the cases (defects of -oxidation of the fat acids, aminoacidopathy, organic aciduria). CONCLUSIONS The preliminary results of the using TMS for the diagnosis of IMD have shown the need for implementation of selective screening IMD using TMS, which is able to conduct diagnosis of 75 metabolites of 49 IMD in single blood spot, which were not detected in RK previously. Taking into the consideration economic expenses of the government, related to the costs of the systematic treatment, medical service, life expectancy and lifelong support of the disabled children with IMD, early detection of orphan metabolic diseases is the vital condition of the decrease of newborn and children death rate, sickness rate and disability. This research study was carried out as a part of a scientific project funded by West Kazakhstan Marat Ospanov Medical University.

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

2008 ◽  
Vol 54 (12) ◽  
pp. 1961-1968 ◽  
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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