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JIMD Reports, Volume 21 pp 45–55Cite as

Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH Gene in Indian Patients

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Part of the book series: JIMD Reports ((JIMD,volume 21))

Abstract

Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of this disease. In this communication, we present the clinical, biochemical and molecular profile of seventeen GA I patients from 15 unrelated families from India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln), c.401A>G (p.Asp134Gly), c.662T>C (p.Leu221Pro), c.881G>C (p.Arg294Pro), c.1173dupG (p.Asn392Glufs*5), c.1238A>G (p.Tyr413Cys) and c.1241A>C (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in Indian patients with GA I. An early diagnosis and timely intervention can improve the underlying prognosis. Molecular confirmation is helpful in providing genetic counselling and prenatal diagnosis in subsequent pregnancy.

Competing interests: None declared

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Acknowledgement

Indian Council of Medical Research for funding

Dr Rita Christopher, NIMHANS Bangalore, Sandor proteomics, Hyderabad

Author information

Authors and Affiliations

  1. Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Neerja Gupta, Pawan Kumar Singh, Shivaram Shastri, Savita Sapra, Sudhisha Dubey & Madhulika Kabra

  2. Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Manoj Kumar & Punit Kaur

  3. Division of Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Sheffali Gulati

  4. Department of Radiology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Atin Kumar

  5. Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Anuja Agarwala

  6. Maulana Azad Medical College, New Delhi, India

    Seema Kapoor & Ankur Singh

  7. Government Medical College, Kozhikode, India

    Mohandas Nair

Authors
  1. Neerja Gupta
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  2. Pawan Kumar Singh
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  5. Sheffali Gulati
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  7. Anuja Agarwala
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Corresponding author

Correspondence to Madhulika Kabra .

Editor information

Editors and Affiliations

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

    Johannes Zschocke

  2. Division of Metabolism and Children’s Research Centre, University Children’s Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  4. Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minnesota, USA

    Marc Patterson

  5. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

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

    Verena Peters

Additional information

Communicated by: Georg Hoffmann

Electronic Supplementary Material

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(DOC 37 kb)

Appendices

Take-Home Message

Exons 11 and 8 of the GCDH gene seem to be the mutational hot spot regions in Indian patients with GA I.

Compliance with Ethics Guidelines

Conflict of Interest

Neerja Gupta, Pawan Kumar Singh, Manoj Kumar, Shivaram Shastri, Sheffali Gulati, Atin Kumar, Anuja Agarwala, Seema Kapoor, Mohandas Nair, Savita Sapra, Sudhisha Dubey, Ankur Singh, Punit Kaur and Madhulika Kabra declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Details of the Contributions of Individual Authors

  • Planning: Neerja Gupta, Pawan Kumar Singh, Sudhisha Dubey, Madhulika Kabra

  • Conducting: Neerja Gupta, Pawan Kumar Singh, Shivaram Shastri, Sheffali, Gulati, Atin Kumar, Anuja Agarwala, Seema Kapoor, Ankur Singh, Mohandas Nair, Savita Sapra, Sudhisha Dubey, Manoj Kumar, Punit Kaur and Madhulika Kabra

  • Reporting: Neerja Gupta, Pawan Kumar Singh, Shivaram Shastri, Sheffali Gulati, Seema Kapoor, Manoj Kumar and Madhulika Kabra

  • Neerja Gupta and Pawan Kumar Singh participated equally and should share “first authorship”.

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Gupta, N. et al. (2014). Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH Gene in Indian Patients. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 21. JIMD Reports, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_377

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  • DOI: https://doi.org/10.1007/8904_2014_377

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-47171-5

  • Online ISBN: 978-3-662-47172-2

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