Abstract
Background:
The aim of this study was to determine the feasibility of performing newborn screening (NBS) of inborn errors of metabolism (IEMs) using tandem mass spectrometry (TMS) and the impact on its detection rate in Malaysia.
Methods:
During the study period between June 2006 and December 2008, 30,247 newborns from 11 major public hospitals in Malaysia were screened for 27 inborn errors of amino acid, organic acid and fatty acid metabolism by TMS. Dried blood spot (DBS) samples were collected between 24 h and 7 days with parental consent. Samples with abnormal results were repeated and the babies were recalled to confirm the diagnosis with follow-up testing.
Results:
Cut-off values for amino acids and acylcarnitines were established. Eight newborns were confirmed to have IEM: two newborns with Maple syrup urine disease (MSUD), two with methylmalonic aciduria (MMA) one with ethylmalonic aciduria, two with argininosuccinic aciduria and one with isovaleric aciduria. Diagnosis was missed in two newborns. The detection rate of IEMs in this study was one in 2916 newborns. The sensitivity and specificity of TMS were 80% and 99%, respectively.
Conclusions:
IEMs are common in Malaysia. NBS of IEMs by TMS is a valuable preventive strategy by enabling the diagnosis and early treatment of IEM before the onset of symptoms aiming at prevention of mental retardation and physical handicap. A number of shortcomings warrant further solution so that in near future NBS for IEMs will become a standard of care for all babies in Malaysia in tandem with the developed world.
Acknowledgments
We thank the Director General of Health Malaysia for permission to publish this article. Our special thanks to Dr. Shahnaz Murad (Director of IMR) for approval of the research grant and Dr. Rohani Md Yasin (Centre Head, SDC) for critical reading of the research proposal and valuable comments. We would like to extend our gratitude to all clinicians, nurses and midwives from the 11 participating hospitals for their valuable contributions in this study. Our gratitude also extends to the staff of Newborn Screening Laboratory in Biochemistry Unit, IMR.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted article and approved submission.
Research funding: This study was funded by Research Grant from Institute for Medical Research, Ministry of Health Malaysia (Grant / Award Number: ‘MRG-2006-004’).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in thestudy design; in the collection, analysis, and interpretationof data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and molecular bases of inherited diseases, 8th ed. New York: McGraw-Hill, 2001.Search in Google Scholar
2. Mak CM, Lee HC, Chan AY, Lam CW. Inborn errors of metabolism and expanded newborn screening: review and update. Crit Rev Clin Lab Sci 2013;50:142–62.10.3109/10408363.2013.847896Search in Google Scholar PubMed
3. Blau N, Hoffmann GF, Leonard J, Clarke JT. Physician’s guide to the treatment and follow-up of metabolic diseases. Heidelberg: Springer, 2005.10.1007/3-540-28962-3Search in Google Scholar
4. Leonard JV. Komrower lecture: treatment of inborn errors of metabolism: a review. J Inherit Metab Dis 2006;29:275–8.10.1007/s10545-006-0273-4Search in Google Scholar PubMed
5. Thong MK, Yunus ZM. Spectrum of inherited metabolic disorders in Malaysia. Ann Acad Med Singapore 2008;37(Suppl 3):66–70.Search in Google Scholar
6. Yunus ZM, Kamaludin DA, Mamat M, Choy YS, Ngu LH. Clinical and biochemical profiles of maple syrup urine disease in malaysian children. JIMD Rep 2012;5:99–107.10.1007/8904_2011_105Search in Google Scholar PubMed PubMed Central
7. Chen BC, Ngu LH, Zabedah MY. Argininosuccinic aciduria: clinical and biochemical phenotype findings in Malaysian children. Malaysian J Pathol 2010;32:87–95.10.1002/path.2690Search in Google Scholar PubMed
8. Chace DH, Hillman SL, Van Hove JL, Naylor EW. Rapid dagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry. Clin Chem 1997;43:2106–13.10.1093/clinchem/43.11.2106Search in Google Scholar
9. Chace DH, Kalas TA, Naylor EW. Use of tandem mass spectrometry for multianalyte screening of dried blood samples from newborns. Clin Chem 2003;49:1797–817.10.1373/clinchem.2003.022178Search in Google Scholar PubMed
10. Clayton PT. Application of mass spectrometry in the study of inborn errors of metabolism. J Inherit Metab Dis 2001;24:139–50.10.1023/A:1010358715835Search in Google Scholar
11. Ghoshal AK, Guo T, Soukhova N, Soldin SJ. Rapid measurement of plasma acylcarnitines by liquid chromatography-tandem mass spectrometry without derivatization. Clinica Chimica Acta 2005;358:104–12.10.1016/j.cccn.2005.02.011Search in Google Scholar PubMed
12. Rashed MS, Bucknall MP, Little D, Awad A, Jacob M, et al. Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles. Clin Chem 1997;43:1129–41.10.1093/clinchem/43.7.1129Search in Google Scholar
13. Yoon HR, Lee KR, Kang S, Lee DH, Yoo HW, et al. Screening of newborns and high-risk group of children for inborn metabolic disorders using tandem mass spectrometry in South Korea: a three-year report. Clinica Chimica Acta 2005;354:167–80.10.1016/j.cccn.2004.11.032Search in Google Scholar PubMed
14. Lim JS, Tan ES, John CM, Poh S, Yeo SJ, et al. Inborn error of metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): an 8 year journey from pilot to current program. Mol Genet Metab 2014;113:53–61.10.1016/j.ymgme.2014.07.018Search in Google Scholar PubMed
15. Niu D-M, Chien Y-H, Chiang C-C, Ho H-C, Hwu W-L, et al. Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan. J Inherit Metab Dis 2010;33(Suppl 2):S295–305.10.1007/s10545-010-9129-zSearch in Google Scholar PubMed
16. Yamaguchi S, Purevsuren J, Hasegawa T, Kobayashi H, Mushimoto Y, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and Expanded Newborn Screening in Japan, Featured presentation at Newborn Screening and Genetic Testing Symposium and the International Society for Neonatal Screening, Atlanta, May 5 to 10, 2013, Available at: http://www.aphl.org/conferences/proceedings/Documents/2013/2013-Newborn-Screening-Symposium/59Yamaguchi.pdf.Search in Google Scholar
17. Shi X-T, Cai J, Wang Y-Y, Tu W-J, Wang W-P, et al. Newborn screening for inborn errors of metabolism in Mainland China: 30 years of experience, JIMD Rep 2012;6:79–83.10.1007/8904_2011_119Search in Google Scholar PubMed PubMed Central
18. McHugh D, Cameron CA, Abdenur JE, Abdulrahman M, Adair O, et al. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project. Genet Med 2011;13:230–54.10.1097/GIM.0b013e31820d5e67Search in Google Scholar PubMed
19. Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, et al. Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Clin Chem 2001;47:1945–55.10.1093/clinchem/47.11.1945Search in Google Scholar
20. Walter JH, Patterson A, Till J, Besley GT, Fleming G, et al. Bloodspot, acylcarnitine and amino acid analysis in cord blood samples: efficacy and reference, data from a large cohort study. J Inherit Metab Dis 2009;32:95–101.10.1007/s10545-008-1047-ySearch in Google Scholar PubMed
21. Vital Statistic Malaysia 2014, population and demography. Available at: https://www.statistics.gov.my/index.php?r=column/cthemeByCat&cat=165&bul_id=akZOby9EYThSQ3V3WHpZSEdjeU50dz09&menu_id=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09.Search in Google Scholar
©2016 Walter de Gruyter GmbH, Berlin/Boston
