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Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan

  • Newborn Screening
  • Published:
Journal of Inherited Metabolic Disease

Abstract

In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.

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Abbreviations

2MBCD:

2-methylbutyryl-CoA dehydrogenase

3-MCC:

3-methylcrotonyl-coenzyme A carboxylase

ASL:

arginiosuccinate lyase

ASS:

argininosuccinate synthetase

BH4:

tetrahydrobiopterin

cblC:

cobalamin C

Cit:

citrulline

CTD:

carnitine transporter defect

CTLN1 or 2:

citrullinemia type 1 or 2

CPT2:

carnitine palmityl transferase II

DHPR:

dihydropteridine reductase

FAO:

fatty acid oxidation

GA 1 or 2:

glutaric acidemia type 1 or 2

HCS:

holocarboxylase synthetase

HPA:

hyperphenylalaninemia

Ile:

isoleucine

IVA:

isovaleric academia

Leu:

leucine

LCHAD:

long-chain 3-hydroxyacyl-CoA dehydrogenase

MCAD:

medium-chain acyl-CoA dehydrogenase

MCD:

multicarboxylase deficiency

Met:

methionine

MMA:

methylmalonic aciduria

MS/MS:

tandem mass spectrometry

PA:

propionic academia

PAH:

phenylalanine hydroxylase

Phe:

phenylalanine

PKU:

phenylketonuria

PTPS:

6-pyruvoyl-tetrahydropterin synthase

SCAD:

short-chain acyl-CoA dehydrogenase

Tyr:

tyrosine

VLCAD:

very-long-chain acyl-CoA dehydrogenase

C0:

free carnitine

C2:

acetylcarnitine

C3:

propionylcarnitine

C4:

isobutyryl and butyrylcarnitine

C5:

isovaleryl and 2-methylbutyrylcarnitine

C5OH:

hydroxyisovalerylcarnitine and 2-methyl-3-hydroxybutyrylcarnitine

C5DC:

glutarylcarnitine

C6:

hexanoylcarnitine

C8:

octanoylcarnitine

C10:

decanoylcarnitine

C10:1:

decenoylcarnitine

C14:1:

tetradecenoylcarnitine

C16:

palmitoylcarnitine

C18:1:

oleylcarnitine

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Authors and Affiliations

  1. Institute of Clinical Medicine, School of Medicine, National Yang Ming University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan

    Dau-Ming Niu

  2. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, 112, Taiwan

    Dau-Ming Niu & Chuan-Hong Kao

  3. Department of Medical Genetics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Yin-Hsiu Chien & Wuh-Liang Hwu

  4. Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Yin-Hsiu Chien & Wuh-Liang Hwu

  5. Chinese Foundation of Health, Taipei, Taiwan

    Chuan-Chi Chiang & Shu-Min Kao

  6. Taipei Institute of Pathology, Taipei, Taiwan

    Hui-Chen Ho & Hung Chiang

  7. Genome Research Center, National Yang-Ming University, Taipei, Taiwan

    Tze-Tze Liu

  8. Department of Medical Research and Education, Taipei Veterans General Hospital, Bldg 201, Section 2, Shih-Pai Rd, Taipei, 112, Taiwan

    Szu-Hui Chiang & Kwang-Jen Hsiao

  9. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

    Kwang-Jen Hsiao

Authors
  1. Dau-Ming Niu
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  2. Yin-Hsiu Chien
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  3. Chuan-Chi Chiang
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  4. Hui-Chen Ho
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  5. Wuh-Liang Hwu
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  6. Shu-Min Kao
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  7. Szu-Hui Chiang
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  8. Chuan-Hong Kao
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  9. Tze-Tze Liu
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  10. Hung Chiang
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  11. Kwang-Jen Hsiao
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Corresponding authors

Correspondence to Dau-Ming Niu or Kwang-Jen Hsiao.

Additional information

Communicated by: Georg Hoffmann

Competing interests: None declared.

Chien YH, Chiang CC and Ho HC made equal contribution as the first author.

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Niu, DM., Chien, YH., Chiang, CC. et al. Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan. J Inherit Metab Dis 33 (Suppl 2), 295–305 (2010). https://doi.org/10.1007/s10545-010-9129-z

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  • DOI: https://doi.org/10.1007/s10545-010-9129-z

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