Skip to main content
SpringerLink
Log in

Newborn Screening for Glutaric Aciduria-II: The New England Experience

  • Invited Articles
  • Chapter
  • First Online:
JIMD Reports - Case and Research Reports, Volume 13

Part of the book series: JIMD Reports ((JIMD,volume 13))

Abstract

Newborn screening (NBS) using tandem mass spectrometry (MS/MS) permits detection of neonates with Glutaric Aciduria-Type II (GA-II). We report follow-up of positive GA-II screens by the New England Newborn Screening Program.

Methods: 1.5 million infants were screened for GA-II (Feb 1999–Dec 2012). Specialist consult was suggested for infants with two or more acylcarnitine elevations suggestive of GA-II.

Results: 82 neonates screened positive for GA-II, 21 weighing > 1.5 kg and 61 weighing ≤ 1.5 kg. Seven (one weighing < 1.5 kg), were confirmed with GA-II. Four of these had the severe form (died < 1 week). The other three have a milder form and were identified because of newborn screening. Two (ages > 5 years) have a G-Tube in place, had multiple hospitalizations and are slightly hypotonic. The third infant remains asymptomatic (9 months old). Two GA-II carriers were also identified. The remaining positive screens were classified as false positives (FP). Six infants (> 1.5 kg) classified as FP had limited diagnostic work-up. Characteristics and outcomes of all specimens and neonates with a positive screen were reviewed, and marker profiles of the cases and FP were compared to identify characteristic profiles.

Conclusion: In addition to the severe form of GA-II, milder forms of GA-II and some GA-II carriers are identified by newborn screening. Some positive screens classified as FP may be affected with a milder form of the disorder. Characteristic GA-II profiles, quantified as GA-II indexes, may be utilized to predict probability of disorder and direct urgency of intervention for positive screens.

Competing interests: None declared

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

C0:

Free carnitine

C10:

Decanoylcarnitine

C10OH:

Hydroxydecanoylcarnitine

C14:

Tetradecanoylcarnitine

C14:1:

Tetradecenoylcarnitine

C2:

Acetylcarnitine

C3:

Propionylcarnitine

C4:

Butyrylcarnitine

C5:

Isovalerylcarnitine

C5DC:

Glutarylcarnitine

C5OH:

Hydroxyisovalerylcarnitine

C6:

Hexanoylcarnitine

C8:

Octonoylcarnitine

DOL:

Day of life

ETF:

Electron transfer flavoprotein

ETF-DH:

Electron transfer flavoprotein dehydrogenase

FAOD:

Fatty acid oxidation defects

FP:

False positive

GA-II:

Glutaric aciduria-type II

MADD:

Multiple acyl-CoA dehydrogenase deficiency

MCAD:

Medium chain acyl-CoA dehydrogenase deficiency

MS/MS:

Tandem mass spectrometry

NBS:

Newborn screening

NENSP:

New England Newborn Screening Program

NICU:

Neonatal intensive care unit

OOR:

Out of range

SCAD:

Short-chain acyl-CoA dehydrogenase deficiency

TP:

True positive

TPN:

Total parental nutrition

VLBW:

Very low birth weight

VLCADD:

Very long chain acyl-CoA dehydrogenase deficiency

References

  • al-Essa MA, Rashed MS, Bakheet SM et al (2000) Glutaric aciduria type II: observations in seven patients with neonatal- and late-onset disease. J Perinatol 20:120–128

    Article  CAS  PubMed  Google Scholar 

  • Bohm N, Uy J, Kiessling M, Lehnert W (1982 Sep) Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II), congenital polycystic kidneys, and symmetric warty dysplasia of the cerebral cortex in two newborn brothers. II. Morphology and pathogenesis. Eur J Pediatr 139(1):60–65

    Article  CAS  PubMed  Google Scholar 

  • Browning MF, Larson C, Strauss A et al (2005) Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects. J Inherit Metab Dis 28(4):545–550

    Article  CAS  PubMed  Google Scholar 

  • Chiong MA, Sim KG, Carpenter K et al (2007 Sep–Oct) Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Mol Genet Metab 92(1–2):109–114

    Google Scholar 

  • Curcoy A, Olsen RK, Ribes A, Trenchs V, Vilaseca MA, Campistol J, Osorio JH, Andresen BS, Gregersen N (2003 Apr) Late-onset form of beta-electron transfer flavoprotein deficiency. Mol Genet Metab 78(4):247–249

    Article  CAS  PubMed  Google Scholar 

  • de Visser M, Scholte HR, Schutgens RB, Bolhuis PA, Luyt-Houwen IE, Vaandrager-Verduin MH, Veder HA, Oey PL (1986 Mar) Riboflavin-responsive lipid-storage myopathy and glutaric aciduria type II of early adult onset. Neurology 36(3):367–372

    Article  PubMed  Google Scholar 

  • Di Donato S, Frerman FE, Rimoldi M et al (1986) Systemic carnitine deficiency due to lack of electron transfer flavoprotein:ubiquinone oxidoreductase. Neurology 36:957–963

    Article  PubMed  Google Scholar 

  • Frerman FE, Goodman SI (1985) Deficiency of electron transfer flavoprotein or electron transfer flavoprotein ubiquinone oxidoreductase in glutaric acidemia type II fibroblasts. Proc Natl Acad Sci USA 82:4517–4520

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Frerman FE, Goodman SI (2001) Defects of electron transfer flavoprotein and electron transfer flavoprotein-ubiquinone oxidoreductase: glutaric aciduria type 2. In: Charles R Scriver, Arthur L Beaudet, William S Sly, David Valle. The metabolic and molecular bases of inherited disease. Vol. 8. McGraw-Hill, New York. pp 2357–2365

    Google Scholar 

  • Goodman SI, Binard RJ, Woontner MR, Frerman FE (2002 Sep–Oct). Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene. Mol Genet Metab 77(1–2):86–90

    Google Scholar 

  • Loehr JP, Goodman SI, Frerman FE (1990) Glutaric acidemia type II: heterogeneity of clinical and biochemical phenotypes. Pediatr Res 27:311–315

    Article  CAS  PubMed  Google Scholar 

  • Millington DS, Kodo N, Norwood D et al (1990) Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J Inherit Metab Dis 13(3):321–324

    Article  CAS  PubMed  Google Scholar 

  • Olsen RK, Andresen BS, Christensen E et al (2003) Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat 22:12–23

    Article  CAS  PubMed  Google Scholar 

  • Olsen RK, Olpin SE, Andresen BS et al (2007) ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain 130:2045–2054

    Article  PubMed  Google Scholar 

  • Online Mendelian Inheritance in Man (OMIM) (2012). Johns Hopkins University, Baltimore, Maryland. MIM Number: 231680

    Google Scholar 

  • Rhead WJ, Wolff JA, Lipson M et al (1987) Clinical and biochemical variation and family studies in the multiple acyl CoA dehydrogenase disorders. Pediatr Res 21:371–376

    Article  CAS  PubMed  Google Scholar 

  • Sahai I (2011) Multicenter validation of algorithms to improve communication of positive newborn screening results. Newborn screening and genetic testing symposium (APHL), San Diego, CA

    Google Scholar 

  • Van Hove JL, Rutledge SL, Nada MA et al (1995) 3-Hydroxyisovalerylcarnitine in 3-methylcrotonyl-CoA carboxylase deficiency. J Inherit Metab Dis 18(5):592–601

    Article  PubMed  Google Scholar 

  • Zytkovicz TH, Fitzgerald EF, Marsden D et al (2001 Nov) 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 47(11):1945–1955

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge the Massachusetts Department of Health, the Maine Department of Health and Human Services, the New Hampshire Department of Health and Human Services, the Rhode Island Department of Health, and the Vermont Department of Health for their partnership and cooperation. Further, the efforts of the treating physicians cannot be underscored. This study was supported in part by Priority Focus I and Priority Focus II funding bound to HRSA Grant U22MC03959.

Author information

Authors and Affiliations

  1. New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain, MA, USA

    I. Sahai, J. Bailey, T. H. Zytkovicz & R. B. Eaton

  2. Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA

    I. Sahai, M. Martin, T. H. Zytkovicz & R. B. Eaton

  3. Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA

    I. Sahai & D. A. Sweetser

  4. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    I. Sahai, P. James, H. L. Levy, E. Neilan & D. A. Sweetser

  5. Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA

    C. L. Garganta

  6. Department of Medicine, Boston Children’s Hospital, Boston, MA, USA

    P. James, H. L. Levy & E. Neilan

  7. Department of Pediatrics, University of Massachusetts Medical Center, Worcester, MA, USA

    M. Martin

  8. Department of Pediatrics, Rhode Island Hospital, Brown University, Providence, RI, USA

    C. Phornphutkul

  9. 305 South St, Jamaica Plain, 02130, MA, USA

    I. Sahai

Authors
  1. I. Sahai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. L. Garganta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Bailey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. James
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. L. Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. Neilan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. Phornphutkul
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D. A. Sweetser
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T. H. Zytkovicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R. B. Eaton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Sahai .

Editor information

Editors and Affiliations

  1. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  2. Clinical Pharmacology Unit, WSU Division of Health Sciences, Spokane, USA

    K. Michael Gibson

  3. Department of Biochemistry Genetics Unit, University of Oxford, Oxford, United Kingdom

    Garry Brown

  4. Department of Pediatrics IGMD, Tulane University Medical Center, New Orleans, Louisiana, USA

    Eva Morava

  5. Center for Child and Adolescent Medicine Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Piero Rinaldo, MD, PhD

Appendices

Synopsis

We report the experience of the New England Newborn Screening Program in identifying individuals at risk for GA-II, the characteristics and outcomes of all specimens and neonates with a positive screen, and long-term outcomes of confirmed cases.

Conflict of Interest

All authors (I Sahai, CL Garganta, J Bailey, P James, HL Levy M Martin, E Neilan, C Phornphutkul, DA Sweetser, TH Zytkovicz and RB Eaton ) declare that they have no conflict of interest.

Informed Consent/Human or Animal Studies

This report summarizes the experience of the New England Newborn Screening Program. This chapter does not contain any studies with human or animal subjects performed by any of the authors.

Authors Attestations

  • The authors have not submitted similar publications previously or simultaneously.

  • All authors have inspected the manuscript.

  • All authors are in agreement for the submission.

  • All authors have been involved in (a) conception and design, or analysis and interpretation of data, and (b) drafting the article or revising it critically for important intellectual content.

Rights and permissions

Reprints and permissions

Copyright information

© 2013 SSIEM and Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Sahai, I. et al. (2013). Newborn Screening for Glutaric Aciduria-II: The New England Experience. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, Volume 13. JIMD Reports, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_262

Download citation

  • DOI: https://doi.org/10.1007/8904_2013_262

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-54148-3

  • Online ISBN: 978-3-642-54149-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation