Is Expanded Newborn Screening Adequate to Detect Indian Biochemical Low Excretor Phenotype Patients of Glutaric Aciduria Type I?

  • Muntaj Shaik
  • Kruthika-Vinod T. P.
  • Mahesh Kamate
  • Vedamurthy A. B.Email author
Original Article



To investigate if expanded newborn screening using tandem mass spectroscopy (TMS) is adequate to detect low excretor phenotype in Indian Glutaric aciduria type I (GA-I) patients.


Ten GA-I patients were investigated for blood glutaryl carnitine (C5DC) levels on dried blood spot (DBS) by tandem mass spectroscopy and urine glutaric acid (GA) and 3-hydroxyglutaric acid (3-OH-GA) by gas chromatography-mass spectroscopy. The student’s T test and Pearson’s correlation were applied to draw a relationship between various biochemical parameters. Further confirmation of low excretors by DNA mutation analysis in the glutaryl CoA dehydrogenase (GCDH) gene was performed by polymerase chain reaction and Sangers sequencing.


Among 10 GA-I patients, 7 patients were found to have high excretor, and 3 were found to have low excretor phenotype. The low excretors were found to have GCDH gene mutations. The mean C5DC levels in high and low excretors were 2.61 ± 2.02 μmol/L and 2.31 ± 1.00 μmol/L, respectively. In high excretors, C5DC levels correlated with GA (r = 0.95). In low excretors, C5DC levels correlated with 3-OH-GA (r = 0.99). No significant difference was found between C5DC levels of high and low excretors (p = 0.82).


The MS/MS, C5DC screening is a sensitive technique and detected 10 GA-I patients. Irrespective of the urine organic acid levels, Indian GA-I patients including low excretors seem to have a significantly elevated C5DC level and well above the stipulated cut-off values and therefore, expanded newborn screening is probably adequate to diagnose them.


Glutaric aciduria type I Glutaryl carnitine Newborn screening Tandem mass spectroscopy Glutaric acid 


Authors’ Contribution

All the authors have revised the manuscript and contributed to the drafting of the article. They confirm that the manuscript is an original version and has not been published in any other scientific journal or elsewhere; MS has performed the biochemical analysis and genetic analysis and drafted the manuscript. MK has been the referral physician for neonatal resuscitation and metabolic and nutritional management of the patient and has validated the results. KVTP and VAB have helped in cross checking the genetic reports and framing the script. All authors read and approved the final manuscript. Prof. Shyam Kumar Vootla, Professor and Chairman, Department of Biotechnology and Microbiology, Karnatak University, Dharwad, is the guarantor for this article.

Compliance with Ethical Standards

Conflict of Interest


Source of Funding

Maulana Azad National Fellowship F1–17.1/2017–18/MANF-2017-18-KAR-75132.


  1. 1.
    Barić I, Baraka K, Maradin M, et al. Glutaric aciduria type 1: an example of the importance of early detection of so-called cerebral organic aciduria. [Article in Croatian]. Lijec Vjesn. 2003;125:312–6.Google Scholar
  2. 2.
    Strauss KA, Puffenberger EG, Robinson DL, Morton DH. Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet. 2003;121C:38–52.Google Scholar
  3. 3.
    Kölker S, Garbade SF, Greenberg CR, et al. Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr Res. 2006;59:840–7.CrossRefGoogle Scholar
  4. 4.
    Vaidyanathan K, Narayanan MP, Vasudevan DM. Organic acidurias: an updated review. Indian J Clin Biochem. 2011;26:319–25.CrossRefGoogle Scholar
  5. 5.
    Babu RP, Bishnupriya G, Thushara PK, et al. Detection of glutaric acidemia type 1 in infants through tandem mass spectrometry. Mol Genet Metabol Rep. 2015;3:75–9.CrossRefGoogle Scholar
  6. 6.
    Fraidakis MJ, Liadinioti C, Stefanis L, et al. Rare late-onset presentation of glutaric aciduria type I in a 16-year-old woman with a novel GCDH mutation. JIMD Rep. 2015;18:85–92.Google Scholar
  7. 7.
    Busquets C, Merinero B, Christensen E, et al. Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct. Pediatr Res. 2000;48:315–22.CrossRefGoogle Scholar
  8. 8.
    Boy N, Mengler K, Thimm E, et al. Newborn screening: a disease-changing intervention for glutaric aciduria type 1. Ann Neurol. 2018;83:970–9.CrossRefGoogle Scholar
  9. 9.
    Hedlund GL, Longo N, Pasquali M. Glutaric acidemia type 1. Am J Med Genet P C Semin Med Genet. 2006;142C:86–94.CrossRefGoogle Scholar
  10. 10.
    Kolker S, Christensen E, Leonard JV, et al. Diagnosis and management of glutaric aciduria type I-revised recommendations. J Inherit Metab Dis. 2011;34:677–94.CrossRefGoogle Scholar
  11. 11.
    Boy N, Mühlhausen C, Maier EM, et al. Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision. J Inherit Metab Dis. 2017;40:75–101.CrossRefGoogle Scholar
  12. 12.
    Heringer J, Boy N, Burgard P, Okun JG, Kolker S. Newborn screening for glutaric aciduria type I: benefits and limitations. Int J Neonatal Screen. 2015;1:57–68.CrossRefGoogle Scholar
  13. 13.
    Horster F, Kolker S, Loeber JG, Cornel MC, Hoffmann GF, Burgard GF. Newborn screening programmes in europe, arguments and efforts regarding harmonisation: focus on organic acidurias. JIMD Rep. 2017;32:105–15.Google Scholar
  14. 14.
    Chace DH, Kalas TA, Naylor EW. Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem. 2003;49:1797–817.CrossRefGoogle Scholar
  15. 15.
    Heringer J, Boy SP, Ensenauer R, et al. Use of guidelines improves the neurological outcome in glutaric aciduria type I. Ann Neurol. 2010;68:743–52.CrossRefGoogle Scholar
  16. 16.
    Wilcken B, Wiley V, Hammond J. Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med. 2003;348:2304–12.CrossRefGoogle Scholar
  17. 17.
    Lindner M, Kölker S, Schulze A, Christensen E, Greenberg CR, Hoffmann GF. Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27:851–9.CrossRefGoogle Scholar
  18. 18.
    Smith WE, Millington DS, Koeberl DK, Lesser PS. Glutaric acidemia, type I, missed by newborn screening in an infant with dystonia following promethazine administration. Pediatrics. 2001;107:1184–7.CrossRefGoogle Scholar
  19. 19.
    Kaur G, Thakur K, Kataria S, et al. Current and future perspective of newborn screening: an Indian scenario. J Pediatr Endocrinol Metab. 2016;29:5–13.CrossRefGoogle Scholar
  20. 20.
    Devi ARR, Naushad SM. Newborn screening in India. Indian J Pediatr. 2004;71:157–60.CrossRefGoogle Scholar
  21. 21.
    Banta-Wright SA, Steiner RD. Tandem mass spectrometry in newborn screening: a primer for neonatal and perinatal nurses. J Perinat Neonatal Nurs. 2004;18:41–58.CrossRefGoogle Scholar
  22. 22.
    Rakheja D, Jones VK, Burlina AB, Bennett MJ. Diagnosis of glutaric acidemia type I: a cautionary note. Lab Med. 2005;36:174–7.CrossRefGoogle Scholar
  23. 23.
    Couce ML, López-Suárez O, Bóveda MD, et al. Glutaric aciduria type I: outcome of patients with early- versus late-diagnosis. Eur J Paediatr Neurol. 2013;17:383–9.CrossRefGoogle Scholar
  24. 24.
    Radha Rama Devi A, Ramesh VA, Nagarajaram HA, Satish SP, Jayanthi U, Lingappa L. Spectrum of mutations in Glutaryl-CoA dehydrogenase gene in glutaric aciduria type I--study from South India. Brain Dev. 2016;38:54–60.CrossRefGoogle Scholar
  25. 25.
    Gupta N, Singh PK, Kumar M, et al. Glutaric acidemia type 1-clinico-molecular profile and novel mutations in GCDH gene in Indian patients. JIMD Rep. 2015;21:45–55.Google Scholar
  26. 26.
    Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q. Role of carnitine in disease. Nutr Metab. 2010;7:30.CrossRefGoogle Scholar
  27. 27.
    Tortorelli S, Hahn SH, Cowan TM, Brewster TG, Rinaldo P, Matern D. The urinary excretion of glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric aciduria type I. Mol Genet Metab. 2005;84:137–43.CrossRefGoogle Scholar
  28. 28.
    Keyser B, Glatzel M, Stellmer F, et al. Transport and distribution of 3-hydroxyglutaric acid before and during induced encephalopathic crises in a mouse model of glutaric aciduria type 1. Biochim Biophys Acta Mol Basis Dis. 2008;1782:385–90.Google Scholar
  29. 29.
    Al-Dirbashi OY, Kölker S, Ng D, et al. Diagnosis of glutaric aciduria type 1 by measuring 3-hydroxyglutaric acid in dried urine spots by liquid chromatography tandem mass spectrometry. J Inherit Metab Dis. 2011;34:173–80.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  1. 1.Department of Biotechnology and MicrobiologyKarnatak UniversityDharwadIndia
  2. 2.Department of NeurochemistryNational Institute of Mental Health and NeurosciencesBengaluruIndia
  3. 3.Department of Pediatrics, Jawaharlal Nehru Medical CollegeKLE UniversityBelgaumIndia

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