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Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases pp 63–83Cite as

Disorders of Glycine, Serine, GABA, and Proline Metabolism

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Abstract

In addition to the role as components of protein synthesis, several amino acids have other functions in the brain such as building blocks of other brain molecules and a role in neurotransmission. Disorders in catabolism of glycine and of proline are known. The disorders of the synthesis of serine and proline cause severe abnormalities. Serine is required for the synthesis of white matter compounds such as specialized lipids, and its deficiency results in severe hypomyelination. Proline is required for the synthesis of connective tissue proteins, and its deficiency results in laxity of skin and joints. Early treatment of synthetic defects such as serine has shown more promise to avoid severe symptoms. Disturbance of the neurotransmitter roles of GABA, glycine, and 4-hydroxybutyric acid results in severe neurological symptoms. The pathophysiology of these disorders is complex, as has been shown in the mouse model of 4-hydroxybutyric aciduria. In most disorders, diagnostic studies rely on careful measurement of metabolites using age-appropriate reference ranges, followed by molecular analysis.

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Authors and Affiliations

  1. Clinical Genetics and Metabolism, The Children’s Hospital, Education 2 South, L28-4122, 13121 E. 17th Avenue, Aurora, CO, 80045, USA

    Johan L. K. Van Hove & Janet A. Thomas

Authors
  1. Johan L. K. Van Hove
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  2. Janet A. Thomas
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Correspondence to Johan L. K. Van Hove .

Editor information

Editors and Affiliations

  1. Department of General Pediatrics, University Children's Hospital, Division of Inborn Metabolic Diseases, Heidelberg, Germany

    Nenad Blau

  2. Laboratory Genetic Metabolic Diseases, University of Amsterdam Academic Medical Centre, Amsterdam, The Netherlands

    Marinus Duran

  3. Section of Clinical Pharmacology, Washington State University, Spokane, Washington, USA

    K Michael Gibson

  4. Division of Metabolism, Department of Pediatric Medicine, Bambino Gesù Children’s Research Hospital, Rome, Italy

    Carlo Dionisi Vici

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Van Hove, J.L.K., Thomas, J.A. (2014). Disorders of Glycine, Serine, GABA, and Proline Metabolism. In: Blau, N., Duran, M., Gibson, K., Dionisi Vici, C. (eds) Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40337-8_5

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  • DOI: https://doi.org/10.1007/978-3-642-40337-8_5

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-40336-1

  • Online ISBN: 978-3-642-40337-8

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