Skip to main content
SpringerLink
Log in

Glutaric aciduria type 1 and neonatal screening: time to proceed—with caution

  • Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The new technology of tandem mass spectrometry is having a significant impact on the diagnostics of inborn metabolic errors. One of the most important aspects of this new technology is the possibility of recognising a whole class of disorders within a single analytical step. Shall this powerful technology be applied to the screening of newborn babies? Careful evaluation of every single disorder that could potentially be identified is needed. In the following, I will present some considerations that concern glutaric aciduria type 1 (MIM 231670; glutaryl-CoA dehydrogenase deficiency).

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

GADH :

glutaryl-CoA dehydrogenase

GA1 :

glutaric aciduria type 1

TMS :

tandem mass spectrometry

References

  1. Altman NR, Rovira MJ, Bauer M (1991) Glutaric aciduria type 1: MR findings in two cases. AJNR 12: 966–968

    CAS  Google Scholar 

  2. Baric I, Zschocke J, Christensen E, Duran M, Goodman SI, Leonard JV, Muller E, Morton DH, Superti-Furga A, Hoffmann GF (1998) Diagnosis and management of glutaric aciduria type I. J Inherit Metab Dis 21: 326–340

    Google Scholar 

  3. Brandt NJ, Gregersen N, Christensen E, Rasmussen K (1978) Glutaric aciduria in two brothers. J Inherit Metab Dis 1: 13–14

    CAS  PubMed  Google Scholar 

  4. Brandt NJ, Gregersen N, Christensen E, Gron IH, Rasmussen K (1979) Treatment of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria). Experience with diet, riboflavin, and GABA analogue. J Pediatr 94: 669–673

    CAS  PubMed  Google Scholar 

  5. Brismar J, Ozand PT (1994) CT and MR of the brain in the diagnosis of organic acidemias. Experiences from 107 patients. Brain Dev 16[Suppl]: 104–124

  6. Collins J, Leonard JV (2000) Natural history of glutaric aciduria type 1. Arch Dis Child 83: 87

    Article  CAS  Google Scholar 

  7. Drigo P, Burlina AB, Battistella PA (1993) Subdural hematoma and glutaric aciduria type 1. Brain Dev 15: 460–461

    Article  CAS  PubMed  Google Scholar 

  8. Greenberg CR, Prasad AN, Dilling LA, Thompson JR, Haworth JC, Martin B, Wood-Steiman P, Seargeant LE, Seifert B, Booth FA, Prasad C (2002) Outcome of the first 3 years of a DNA-based neonatal screening program for glutaric acidemia type 1 in Manitoba and northwestern Ontario, Canada. Mol Genet Metab 75: 70–78

    Article  CAS  PubMed  Google Scholar 

  9. Haworth JC, Booth FA, Chudley AE, de Groot GW, Dilling LA, Goodman SI, Greenberg CR, Mallory CJ, McClarty BM, Seshia SS et al (1991) Phenotypic variability in glutaric aciduria type I: report of fourteen cases in five Canadian Indian kindreds. J Pediatr 118: 52–58

    CAS  PubMed  Google Scholar 

  10. Hoffmann GF, Zschocke J (1999) Glutaric aciduria type I: from clinical, biochemical and molecular diversity to successful therapy. J Inherit Metab Dis 22: 381–391

    Article  CAS  PubMed  Google Scholar 

  11. Hoffmann GF, Trefz FK, Barth PG, Böhles HJ, Biggemann B, Bremer HJ, Christensen E, Frosch M, Hanefeld F, Hunneman DH et al (1991) Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy. Pediatrics 88: 1194–1203

    CAS  PubMed  Google Scholar 

  12. Hoffmann GF, Athanassopoulos S, Burlina AB, Duran M, de Klerk JB, Lehnert W, Leonard JV, Monavari AA, Muller E, Muntau AC, Naughten ER, Plecko-Starting B, Superti-Furga A, Zschocke J, Christensen E (1996) Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 27: 115–123

    CAS  PubMed  Google Scholar 

  13. Kohler M, Hoffmann GF (1998) Subdural haematoma in a child with glutaric aciduria type I. Pediatr Radiol 28: 582

    Article  CAS  PubMed  Google Scholar 

  14. Kolker S, Ahlemeyer B, Krieglstein J, Hoffmann GF (1999) 3-Hydroxyglutaric and glutaric acids are neurotoxic through NMDA receptors in vitro. J Inherit Metab Dis 22: 259–262

    CAS  PubMed  Google Scholar 

  15. Kolker S, Ahlemeyer B, Krieglstein J, Hoffmann GF (2000) Maturation-dependent neurotoxicity of 3-hydroxyglutaric and glutaric acids in vitro: a new pathophysiologic approach to glutaryl-CoA dehydrogenase deficiency. Pediatr Res 47: 495–503

    CAS  PubMed  Google Scholar 

  16. Kolker S, Ramaekers VT, Zschocke J, Hoffmann GF (2001) Acute encephalopathy despite early therapy in a patient with homozygosity for E365K in the glutaryl-coenzyme A dehydrogenase gene. J Pediatr 138: 277–279

    Article  CAS  PubMed  Google Scholar 

  17. Kolker S, Kohr G, Ahlemeyer B, Okun JG, Pawlak V, Horster F, Mayatepek E, Krieglstein J, Hoffmann GF (2002) Ca(2+) and Na(+) dependence of 3-hydroxyglutarate-induced excitotoxicity in primary neuronal cultures from chick embryo telencephalons. Pediatr Res 52: 199–206

    Article  PubMed  Google Scholar 

  18. Kolker S, Okun JG, Ahlemeyer B, Wyse AT, Horster F, Wajner M, Kohlmuller D, Mayatepek E, Krieglstein J, Hoffmann GF (2002) Chronic treatment with glutaric acid induces partial tolerance to excitotoxicity in neuronal cultures from chick embryo telencephalons. J Neurosci Res 68: 424–431

    Article  CAS  PubMed  Google Scholar 

  19. Lopez AD, Murray CC (1998) The global burden of disease, 1990–2020. Nat Med 4: 1241–1243

    Article  CAS  PubMed  Google Scholar 

  20. Lutcherath V, Waaler PE, Jellum E, Wester K (2000) Children with bilateral temporal arachnoid cysts may have glutaric aciduria type 1 (GAT1); operation without knowing that may be harmful. Acta Neurochir (Wien) 142: 1025–1030

    Google Scholar 

  21. Mandel H, Braun J, Elpeleg O, Christensen E, Berant M (1991) Glutaric aciduria type I. Brain CT features and a diagnostic pitfall. Neuroradiology 33: 75–78

    CAS  PubMed  Google Scholar 

  22. Martinez-Lage JF, Casas C, Fernandez MA, Puche A, Rodriguez-Costa T, Poza M (1994) Macrocephaly, dystonia, and bilateral temporal arachnoid cysts: glutaric aciduria type 1. Childs Nerv Syst 10: 198–203

    CAS  PubMed  Google Scholar 

  23. Monavari AA, Naughten ER (2000) Prevention of cerebral palsy in glutaric aciduria type 1 by dietary management. Arch Dis Child 82: 67–70

    Article  CAS  PubMed  Google Scholar 

  24. Naylor EW, Chace DH (1999) Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol 14[Suppl 1]: S4–S8

  25. Niiyama S, Koelker S, Degen I, Hoffmann GF, Happle R, Hoffmann R (2001) Acrodermatitis acidemica secondary to malnutrition in glutaric aciduria type I. Eur J Dermatol 11: 244–246

    CAS  PubMed  Google Scholar 

  26. Osaka H, Kimura S, Nezu A, Yamazaki S, Saitoh K, Yamaguchi S (1993) Chronic subdural hematoma as an initial manifestation of glutaric aciduria type 1. Brain Dev 15: 125–127

    Article  CAS  PubMed  Google Scholar 

  27. Schwappach DL (2002) Resource allocation, social values and the QALY: a review of the debate and empirical evidence. Health Expect 5: 210–222

    Article  PubMed  Google Scholar 

  28. Superti-Furga A, Hoffmann GF (1997) Glutaric aciduria type 1 (glutaryl-CoA-dehydrogenase deficiency): advances and unanswered questions. Report from an international meeting. Eur J Pediatr 156: 821–828

    Article  CAS  PubMed  Google Scholar 

  29. Thomason MJ, Lord J, Bain MD, Chalmers RA, Littlejohns P, Addison GM, Wilcox AH, Seymour CA (1998) A systematic review of evidence for the appropriateness of neonatal screening programmes for inborn errors of metabolism. J Public Health Med 20: 331–343

    CAS  PubMed  Google Scholar 

  30. Tilford JM (2002) Cost-effectiveness analysis and emergency medical services for children: issues and applications. Ambul Pediatr 2: 330–336

    PubMed  Google Scholar 

  31. Trefz FK, Hoffmann GF, Mayatepek E, Lichter-Konecki U, Weisser J, Otten A, Wendel U, Rating D, Bremer HJ (1991) Macrocephaly as the initial manifestation of glutaryl-CoA-dehydrogenase deficiency (glutaric aciduria type I). Monatsschr Kinderheilkd 139: 754–758

    CAS  PubMed  Google Scholar 

  32. Ullrich K, Flott-Rahmel B, Schluff P, Musshoff U, Das A, Lucke T, Steinfeld R, Christensen E, Jakobs C, Ludolph A, Neu A, Roper R (1999) Glutaric aciduria type I: pathomechanisms of neurodegeneration. J Inherit Metab Dis 22: 392–403

    CAS  PubMed  Google Scholar 

  33. Wilson JM and Jungner YG (1968) Principles and practice of mass screening for disease. Bol Oficina Sanit Panam 65: 281–393

    CAS  PubMed  Google Scholar 

  34. Woelfle J, Kreft B, Emons D, Haverkamp F (1996) Subdural hemorrhage as an initial sign of glutaric aciduria type 1: a diagnostic pitfall. Pediatr Radiol 26: 779–781

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I am grateful to Drs. Cheryl Greenberg, Georg Hoffmann, Ania Muntau, Adelbert Roscher, Bridget Wilcken, and several members of the Metab-L E-mail community for sharing their thoughts and experiences on glutaric aciduria and neonatal screening.

Author information

Authors and Affiliations

  1. Division of Molecular Paediatrics, CI-02–33, Centre Hospitalier Universitaire Vaudois, 1011 , Lausanne, Switzerland

    Andrea Superti-Furga

Authors
  1. Andrea Superti-Furga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Superti-Furga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Superti-Furga, A. Glutaric aciduria type 1 and neonatal screening: time to proceed—with caution. Eur J Pediatr 162 (Suppl 1), S17–S20 (2003). https://doi.org/10.1007/s00431-003-1344-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-003-1344-2

Keywords

Search

Navigation