Recordati Rare Diseases Academy

Advancing knowledge in rare diseases:
independent, professional, education and training

Synaptic metabolism and brain circuitries in IEM: exploring old and new disorders

  • Increase
  • Decrease
  • Normal
Barcelona, Spain 16 – 18 November 2017
Wednesday, December 7, 2016

The synapse is a highly specialized structure with specific chemical composition and metabolic functions that are necessary for an appropriate neuronal communication and brain development. Neurometabolic diseases are genetic conditions that lead to abnormal concentration and function of different molecules in the brain. Most of them disturb crucial pre and post-synaptic functions and therefore impair neural connectivity and brain circuitries leading to symptoms such as intellectual disability, neuropsychiatric signs, epilepsy, and movement disorders.

Describing how neurometabolic diseases target synapses, synaptic plasticity, and other functions such as excitability and synaptic signaling is a challenge that has been scarcely investigated. Most of our knowledge stays at the “pre-synaptic level” with the description of the biosynthesis and catabolic pathways. In fact most neurometabolic diseases described so far are “pre-synaptic and astrocytic conditions”. However, little is known about the role of very well-known molecules in inborn errors of metabolism such as lactate, ATP, amino acids and lipids, in plasticity, learning functions and excitability, acting through different receptors and signaling pathways. Molecules derived from a particular biochemical pathway at the presynaptic level have in general a continuation at the post-synaptic level and a glia interaction. Should we then consider trans and peri-synaptic communication in the description of whole biochemical pathways in neurometabolic diseases instead of stopping at the pre-synaptic neuron or at the astrocytic level?
Additionally, disrupted synaptic communication are rarely confined to a single locus; instead, they often spread via axonal pathways to influence other neuronal subtypes and anatomic regions, the so-called connectome.

The synaptic approach offers new ways of understanding brain dysfunction and symptoms from a more mechanistic and functional point of view. It integrates our classical metabolic approach into the fields of cellular neurobiology and modern neuroscience. Moreover the description of new disorders and new therapeutic approaches are opened.


  • To learn the basis of neuronal communication in IEM and to understand that this is not restricted to the synthesis, catabolism and transport of the “classic neurotransmitters”.
  • To introduce new categories of neurometabolic diseases based on the description of biochemical pathways, trafficking and signaling functions at the synapse, and to recognize the main clinical manifestations.
  • To learn how neurometabolic diseases affect the brain as a whole system through the study of neuronal connectivity.
  • Insight into new therapeutic strategies such as neuromodulation in IEM.

Institutes of main organisers - providers

  • Sant Joan de Déu Hospital, Esplugues de Llobregat, Barcelona
  • Centre for Childhood and Adolescent Medicine, University Hospital Heidelberg

Scientifc Organising Committee

  • Angeles Garcia-Cazorla, Barcelona
  • Thomas Opladen, Heidelberg
  • Alex Bayès, Barcelona
  • Xavier Altafaj, Barcelona
  • Josep Rizo, Dallas

Contact RRD Foundation

Cecilia Kellquist
Recordati Rare Diseases Fondation d'entreprise
Immeuble ‘Le Wilson’
70 avenue du Général de Gaulle
92800 PUTEAUX, France
Telephone : +33 1 47 73 86 11
Fax : +33 1 49 00 18 00
Email :


Day 1

14:00 Welcome
14:15 The Synaptic Scenario

​1. The synapse: a functional unit in the nervous system. Principles of synaptic communication.
J Rizo. University of Texas Southwestern, Dallas

2-Metabolic characteristics of the synapse: the highly specific chemical compartmentalisation and function.
A Garcia-Cazorla. HSJD, Barcelona

15:30 Synaptic dysfunction in IEM: a global approach

1-Synaptic pathways in intermediary metabolism (UCD, AA defects and other small molecules)
S. Koelker. University of Heidelberg.

2-Synaptic pathways in energy defects (the role of glucose, lactate, ATP…)
Marín-Valencia I. University of Rockefeller, NY

3-Synaptic pathways in defects of complex molecules (focused on complex lipid defects)
F. Mochel. Salpetrière, Paris

4-Application of this approach for clinicians?
Presentation of practical examples (different participants)

Day 2

08:30 Synaptic dysfunction: neuronal structure, cellular and biochemical pathways meet together

1-Disorders of the pre-synaptic terminal (8:30-10:30):
1.1 Pre-synaptic diseases. A. García-Cazorla. HSJD, Barcelona
1.2 Neurological manifestations. E. Cortès. HSJD, Barcelona

Clinical cases (participants)

2-Disorders of the inter-synaptic and post-synaptic space (11-13 h)
2.1- Post- and intersynaptic diseases. Speaker to be defined
2.2- Neurological manifestations. M. Kurian (London)

Clinical cases (participants)

14:00 Investigating synaptic function and dysfunction (proposal: each participant could attend 2 workshops)

1-From synaptic dysfunction to neuronal circuitries (focused in IEM): Advanced brain image techniques.
P.Rodrigues ( Mintlabs. Boston/Barcelona)

2-New diagnostic tools: NGS, proteomics and metabolomics.
A. Bayès, R. Artuch. Barcelona

3-Neuromodulation of brain connectivity.
Roi Cohen Kadosh. Oxford, UK

​4-How to study receptor trafficking and synaptic signaling.
Laurent Groc, U. Bordeaux and X. Altafaj. Barcelona

Day 3

09:00 Molecules involved in synaptic communication: beyond classical neurotransmitters

Disorders of growth factors, peptides and other signaling molecules
Sofia Duarte. Lisbon

Clinical cases (participants)

10:00 Synaptic therapies

1-Pharmacological options to enhance neuronal plasticity and improve cognitive functions. Is this approach useful in IEM?
Frenguelli BG, Warwick, UK

2-iPSCs as model for investigation and development of therapies in synaptic transmission
S. Jung-Klawitter. Heidelberg

11:00 Clinical research and patient-centered resources

1-Natural course of neurotransmitter disordes: Database-based research
T. Opladen. Heidelberg

2-The patients view: small molecules, big effect.
By a patient association representative

Registration details

Target audience and participant profile

The target audience of this course involves metabolic physicians, paediatricians, neurologists and paediatric neurologists as well as laboratory neuroscientists, biochemical geneticists, biochemists and laboratory geneticists. Participants are expected to have prior knowledge about the field, practical experience with diagnosis treatment, and/or basic research is recommended.

Participants are expected to present a case report relevant to the theme of the course; cases with diagnostic and/or therapeutic dilemmas are especially welcome.


The standard course fee of 450€ covers:

  • 2 nights hotel accommodation including breakfast
  • Lunch, coffee and dinner during the course

A local fee of 315€ is granted if accommodation is not needed.

Participants are responsible for their own travel arrangements to and from the course. Fees are not refundable

Registration process and deadline

The registration form should be completed on-line and submitted with your curriculum vitae in English. No payment is required at this stage.

Deadline for registration is 16th of September 2017.

Selection criteria and review process

Candidates will be selected based on their background and experience.
The scientific organising committee will review the applications and select participants.
Selection decisions will be announced within 10 days following the deadline for registration.

CME accreditation:

An application will be made for to the EACCME for CME accreditation.