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Nonketotic Hyperglycinemia (Glycine Encephalopathy) and Lipoate Deficiency Disorders

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Inborn Metabolic Diseases

Zusammenfassung

Nonketotic hyperglycinemia (NKH) is caused by defective glycine cleavage enzyme activity. Classic NKH is caused by mutations in protein coding genes (GLDC and AMT). Disorders of lipoate synthesis and transport are caused by mutations in LIAS, BOLA3, NFU1, GLRX5, ISCA2, IBA57, LIPT1, and LIPT2 and can affect glycine metabolism referred to as variant NKH. Patients with the severe form of classic NKH have minimal development and develop therapy resistant epilepsy. Patients with the attenuated form of classic NKH make variable developmental progress, and present with attention deficits, hyperactivity, chorea, and episodic lethargy. Treatment consists of reduction of glycine levels with benzoate and sometimes diet, and of blocking the excitatory effect of glycine on NMDA receptors with either dextromethorphan or ketamine. Therapy is most effective in patients with attenuated NKH where it can improve development particularly when treatment is initiated early. High levels of CSF glycine and presence of brain malformations are indicative of severe classic NKH, whereas low CSF:plasma glycine ratios, onset after 4 months, or absence of epilepsy are indicators of attenuated classic NKH. A specific pattern of diffusion restriction on brain MRI is nearly always present in the first months of life and is useful in distinction with non-genetic causes of elevated CSF glycine.

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Authors and Affiliations

  1. Anschutz Medical Campus, University of Colorado Denver, East 17th Avenue, L28-4122, Aurora, CO 80045, USA

    Johann L.K. Van Hove

  2. Department of Pediatric and Adolescent Medicine Villa Metabolica, University Medical Center Mainz, Langenbeckstr. 1, 55131, Mainz, Germany

    Julia B. Hennermann

  3. Anschutz Medical Campus, University of Colorado Denver, East 17th Avenue, L28-4110, Aurora, CO 80045, USA

    Curtis R. Coughlin II

Authors
  1. Johann L.K. Van Hove
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  2. Julia B. Hennermann
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  3. Curtis R. Coughlin II
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Corresponding authors

Correspondence to Johann L.K. Van Hove , Julia B. Hennermann or Curtis R. Coughlin II .

Editor information

Editors and Affiliations

  1. Department of Neurology, Neurometabolic Unit, Hôpital Pitié Salpêtrière, Paris, France

    Jean-Marie Saudubray

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

    Matthias R. Baumgartner

  3. Willink Biochemical Genetics Unit Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK

    John Walter

  4. Central Manchester University Hospitals NHS Foundation Trust, St Mary‘s Hospital, Manchester, UK

    John Walter

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Van Hove, J.L., Hennermann, J.B., Coughlin II, C.R. (2016). Nonketotic Hyperglycinemia (Glycine Encephalopathy) and Lipoate Deficiency Disorders. In: Saudubray, JM., Baumgartner, M., Walter, J. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49771-5_23

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  • DOI: https://doi.org/10.1007/978-3-662-49771-5_23

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-49769-2

  • Online ISBN: 978-3-662-49771-5

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