Journal of Inherited Metabolic Disease

, Volume 41, Issue 6, pp 1065–1075 | Cite as

Synaptic metabolism: a new approach to inborn errors of neurotransmission

  • Alba Tristán-Noguero
  • Àngels García-CazorlaEmail author


To date, inborn errors of neurotransmitters have been defined based on the classic concept of inborn error of metabolism (IEM), and they include defects in synthesis, catabolism, and transport pathways. However, the omics era is bringing insights into new diseases and is leading to an extended definition of IEM including new categories and mechanisms. Neurotransmission takes place at the synapse, the most specialized tight junction in the brain. The concept of “synaptic metabolism” would point to the specific chemical composition and metabolic functions of the synapse. Based on these specialized functions, we aim to provide a tentative overview about the major categories of IEM susceptible to affect neurotransmission. Small molecule defects (biogenic amines and amino acids) and energy defects are amongst the most prevalent diseases reported to disturb the concentration of CSF neurotransmitters. In these IEM, the neurological phenotypes have been largely described. Disorders of complex molecules are not typically considered as diseases affecting neurotransmission. However, most of them have been recently discovered and are involved in intracellular vesiculation, trafficking, processing, and quality control mechanisms. In this large group, neurotransmission is affected in disorders of chaperones and autophagy, disorders of the synaptic vesicle, and diseases affecting pre-synaptic membranes (synthesis and remodeling of complex lipids, defects of glycosylation). Disorders of the vesicle pools, receptor trafficking, and the chronobiology of neurotransmission are potentially emerging new categories. Finally, although not considered as IEM, channelopathies are a large group of diseases disturbing neurotransmitter homeostasis. New CSF biomarkers will probably contribute to improve the diagnosis of these disorders and find new therapeutic targets.


Synaptic metabolism Inborn errors of metabolism Inborn errors of neurotransmitters Extended concept of IEM Synaptopathies neurotransmitters 


Compliance with ethical standards

This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of interest

A. Tristán-Noguero and À. García-Cazorla declare that they have no conflict of interest.

Informed consent

Not applicable.

Animal rights

Not applicable.


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Copyright information

© SSIEM 2018

Authors and Affiliations

  • Alba Tristán-Noguero
    • 1
  • Àngels García-Cazorla
    • 1
    • 2
    • 3
    Email author
  1. 1.Synaptic Metabolism Laboratory, Department of Neurology, Fundació Sant Joan de DéuInstitut Pediàtric de RecercaBarcelonaSpain
  2. 2.Neurology DepartmentHospital Sant Joan de DéuEspluguesSpain
  3. 3.Neurometabolic Unit and Synaptic Metabolism Lab. Department of Neurology, Institut Pediàtric de RecercaHospital Sant Joan de Déu and CIBERER (ISCIII)BarcelonaSpain

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