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Disorders of Neurotransmission

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Inborn Metabolic Diseases

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Zusammenfassung

This chapter deals primarily with inborn errors of neurotransmitter metabolism. Defects of their receptors and transporters are also discussed. Three defects of GABA catabolism have been reported: GABA transaminase deficiency (very rare, severe, and untreatable), succinic semialdehyde dehydrogenase (SSADH) deficiency, and homocarnosinosis. Hyperekplexia is usually due to a dominantly inherited defect of the α1 subunit of the glycine receptor which causes excessive startle responses, and is treatable with clonazepam. Mutations in GABAA receptor are a cause of dominantly inherited epilepsy while mutations in glutamate receptors associate with neurodevelopmental and psychiatric disorders. Three transportopathies are reported: mitochondrial glutamate transporter defect, which is a cause of severe epileptic encephalopathy, and diseases that produce early parkinsonism-dystonia: dopamine transporter defect and vesicular monoamine transporter type 2 defect. Six disorders of monoamine metabolism are discussed: Tyrosine hydroxylase (TH) deficiency impairs synthesis of dihydroxyphenylalanine (L-dopa) and causes a neurological disease with prominent extrapyramidal signs, and a variable response to L-dopa. The clinical hallmark of dopamine β-hydroxylasedeficiency is severe orthostatic hypotension with sympathetic failure. The other disorders of monoamine metabolism involve both catecholamine and serotonin metabolism. Aromatic L-amino acid decarboxylase (AADC) is located upstream of the neurotransmitter amines; treatment can be challenging. Monoamine-oxidase A (MAO-A) deficiency, located downstream, mainly causes behavioral disturbances; no effective treatment is known. Guanosine triphosphate cyclohydrolase-I (GTPCH-I) and Sepiapterin reductase (SR) deficiencies are pterin disorders upstream of L-dopa and 5-hydroxytryptophan (5-HTP) with normal baseline phenylalaninemia and effective treatment (especially GTPCH-I deficiency).

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Authors and Affiliations

  1. Servicio de Neurologia, Hospital Sant Joan de Deu and CIBERER-ISCIII, Passeig Sant Joan de Deu 2, 8950, Barcelona, Spain

    Angels Garcia-Cazorla

  2. Clinical Biochemistry department, Hospital Sant Joan de Déu and CIBERER-ISCIII, Paseo de Sant Joan de Déu 2, 8950, Barcelona, Spain

    Rafael Artuch

  3. Allen I. White Professor and Chair, Experimental and Systems Pharmacology, Washington State University, College of Pharmacy, Spokane, WA, USA

    K. Michael Gibson

Authors
  1. Angels Garcia-Cazorla
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  2. Rafael Artuch
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  3. K. Michael Gibson
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Correspondence to Angels Garcia-Cazorla or Rafael Artuch .

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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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Garcia-Cazorla, A., Artuch, R., Gibson, K.M. (2016). Disorders of Neurotransmission. In: Saudubray, JM., Baumgartner, M., Walter, J. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49771-5_29

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  • DOI: https://doi.org/10.1007/978-3-662-49771-5_29

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