Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8year journey from pilot to current program

Lim, Joel Kian Boon; Tan, Ee Shien; John, Catharine; Poh, Sherry; Yeo, SinKoo; Ang, J.S.M.; Adakalaisamy, P.; Rozalli, R.A.; Hart, Claire; Ranieri, Enzo; Rajadurai, Victor Samuel; Cleary, Maureen; Goh, Denise

doi:10.1016/j.ymgme.2014.07.018

Cited by 63 publications

(74 citation statements)

References 19 publications

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“…Several recent reports review NBS expansion activities across the region. [141][142][143][144][145][146][147][148][149] At the time or our 2007 report, 6 only Australia, New Zealand, and Taiwan included expanded metabolic screening with MS/MS in their screening panels. 6 Since that time, other countries in the Asia Pacific region have expanded to include not only additional metabolic screening, but also a number of other conditions not in their panels at that time.…”

Section: Asia Pacificmentioning

confidence: 99%

Current status of newborn screening worldwide: 2015

Therrell

Padilla

Loeber³

et al. 2015

Seminars in Perinatology

441

418

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Section: Asia Pacificmentioning

confidence: 99%

Current status of newborn screening worldwide: 2015

Therrell

Padilla

Loeber³

et al. 2015

Seminars in Perinatology

441

418

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“…The incidence of IEMs detected varies greatly in different countries. For example, the incidence of IEM reported in Korea was 1/2000, 1/3159 in Singapore, 1 /3600 in India, 1/2400 in Germany, 1/2396 in Italy, and 1/4300 in America . The highest reported incidence of IEM was in the Arab nations (Saudi Arabia 1/1381, Lebanon 1/1482, Egyptian 1/1286) …”

Section: Discussionmentioning

confidence: 99%

Expanded newborn screening for inborn errors of metabolism by tandem mass spectrometry in newborns from Xinxiang city in China

Guo

Zhang

et al. 2020

Clinical Laboratory Analysis

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Abbreviations: HPA, hyperphenylalaninemia; IEM, inborn errors of metabolism; IVA, isovaleric academia; MMA, methylmalonic academia; MS/MS, tandem mass spectrometry; MSUD, maple syrup urine disease; PCD, primary carnitine deficiency; SCAD, short-chain acyl-CoA dehydrogenase deficiency. AbstractBackground: Tandem mass spectrometry is a powerful technology available in China over the last 15 years. The development of tandem mass spectrometry had made it possible to rapidly screen newborns for inborn errors of metabolism. The aim of this study was to determine the birth incidence of inborn errors of metabolism through expanded screening of newborns by tandem mass spectrometry in Xinxiang area.Methods: Dried blood spots from 50 112 newborns were assessed for inborn errors of metabolism by tandem mass spectrometry. The diagnoses were confirmed based on the clinical features, conventional laboratory tests, and the organic acid levels tested in urine by gas chromatography-mass spectrometry. Results:The study findings revealed that 31 newborns were diagnosed with inborn errors of metabolism. The total incidence rate of inborn errors of metabolism was 1/1617, and these included 16 cases of amino acid disorders (51.6%), nine cases of organic acid disorders (29.0%), and 6 (19.4%) cases of fatty acid beta-oxidation disorders. Conclusions:The screening for the incidence of inborn errors of metabolism in Xinxiang area showed that the rate was higher than previously reported. This study provides valuable data which may be useful in facilitating improvements in the expansion of screening to enable early diagnosis and treatment of inborn errors of metabolism before the onset of symptoms. K E Y W O R D S amino acid disorders, fatty acid beta-oxidation disorders, inborn errors of metabolism, organic acid disorders, tandem mass spectrometry S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.

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“…All the diseases are included in the U.S. federally recommended uniform screening panel, with five belonging to the core panel, and the other five to the secondary panel, consisting of common rare diseases that have an average prevalence of 1:10,000 ~ 1:50,000 except tyrosinemia type III (TYRIII) that was reported very rare [18][19][20].…”

Section: Molecular Diagnostic Outcomementioning

confidence: 99%

“…Functional prediction (Supplemental Table 4) revealed that all but one of the seven VUS mutations present a certain degree of pathogenic tendency, among which four have coincident biochemical features that result in positive diagnosis, one (c.286A>G) has coincident biochemical features that result in high-risk diagnosis (recessive carrier), and one (c.1711C>A) has discrepant biochemical features that result in high-risk diagnosis (homozygote). Interestingly, the (c.1711C>A) mutation came from the CPT2 gene, corresponding to carnitine palmitoyltransferase II deficiency (CPTII) that is usually suspected with elevated C16 and/ or C18:1 acylcarnitine [19,20]. However, the homozygous (c.1711C>A) was found correlating to a measured decrease (in both primary and confirmatory tests) of free carnitine that is indicative of carnitine uptake defect (CUD), resulting in a CUD-negative diagnosis made by our client (data not shown).…”

Section: Tngs Assaymentioning

confidence: 99%

“…On the other hand, many IEMs are clinically heterogeneous that the molecular diagnosis is not always practically helpful [34] because of the imperfect penetrance of each individual genotype. It has been reported that the implementation of TMS screening program has led to more identified cases bearing certain disorders of which most subjects are asymptomatic throughout their life [9,[20][21][22]. The environmental/maternal/ethnic effect as well as miscellaneous manifestation also complicated the genotype/phenotype correlation [35][36][37][38].…”

Section: Limitationmentioning

confidence: 99%

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Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening

Qian

Wang

Liu

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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Background: Tandem mass spectrometry (TMS)-based newborn screening has been proven successful as one of the public healthcare programs, although the practicability has not yet been specifically addressed. Methods: Sixty residual dried blood spot (DBS) specimens from confirmation/diagnosis-insufficient cases discovered by TMS screening were analyzed by targeted next generation sequencing (TNGS) assay. Results: In total, 26, 11, 9, and 14 cases were diagnosed as positive, high risk, low risk, and negative, respectively. Conclusions: Applying the DBS-based TNGS assay for the accurate and rapid diagnosis of inborn errors of metabolism (IEMs) is feasible, competent, and advantageous, enabling a simplified TMS screening-based, TNGS assay-integrated newborn screening scheme highlighting an efficient, executable, and one-step screening-to-diagnosis workflow.

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Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8year journey from pilot to current program

Cited by 63 publications

References 19 publications

Current status of newborn screening worldwide: 2015

Current status of newborn screening worldwide: 2015

Expanded newborn screening for inborn errors of metabolism by tandem mass spectrometry in newborns from Xinxiang city in China

Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening

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