Classification and diagnostic approach of IEM
affecting the synthesis and remodelingof complex lipids
Paris, 24 – 26 June 2015
Classification and diagnostic approach of IEM affecting the synthesis and remodeling of complex lipids
PROVIDER ORGANISATIONS:
La Pitié-Salpêtriére Hospital, Pierre et Marie Curie University Paris VI
The Pitié-Salpêtrière is the largest hospital in France with over 1600 beds and 171 ambulatory beds. The hospital has a long history which originates from a “bureau of poverty” created in 1544 to keep beggars from the streets of Paris and in 1612, Marie de Medicis created the hospice “Notre Dame de la Pitié” to host the poor. Later, through the eminent Dr. Philippe Pinel, the Salpêtrière became world famous as a psychiatric centre. A century later, Jean-Martin Charcot was credited as the founder of modern neurology. The Pitié-Salpêtrière is now one of the biggest university hospitals in Europe, with departments focusing on most major medical specialties and research. Neurology and psychiatry are well represented through the «Brain and Spinal Cord institute”, constructed in 2010, is a major neurological and psychiatric research centre. The department of neurology has developed a unit dedicated to neurological aspects of inherited metabolic diseases. This neurometabolic unit has four main goals: 1) to care for patients previously managed in paediatric metabolic centres 2) to diagnose late onset forms of IEM, 3) to develop teaching and 4) to develop research in metabolic aspects of nervous system diseases. The hospital has an academic partnership with Pierre and Marie Curie School of Medicine (University Paris VI).
University CHILDREN’S HOSPITAL, Zurich
The University Children’s Hospital in Zurich is not only the largest paediatric clinic in Switzerland but also one of the leading centres for paediatric and youth medicine in Europe. Which is why patients come from all corners of Switzerland and abroad. Besides undertaking the normal tasks of a university hospital, we also train doctors to become specialists in their field. Therefore our children’s hospital houses the first and as yet only research centre in Switzerland that is solely dedicated to paediatric research.
Areas of specialisation: the University Children’s Hospital Zurich is the largest pediatric centre for many services including heart problems, bone marrow transplant and burns. With our comprehensive service range of 32 medical sub-specialisations, we are on par with the largest children’s clinics in the world. In fact, our medical and surgical clinic’s service range is typical of larger university hospitals.
ACADEMIC MEDICAL CENTER, University of amsterdam
The Academic Medical Center (AMC) was founded in 1983, when two hospitals from the Amsterdam city centre, the Wilhelmina Gasthuis and the Binnengasthuis, merged with the medical faculty of the University of Amsterdam. Five years later, the Emma Children’s Hospital also became a part of the new university hospital.
The AMC is one of the eight university medical centres in the Netherlands and has metabolic disorders as one of its core areas of research and patient care. In the area of metabolic diseases, research concentrates on unravelling illness attributed to fundamental defects in metabolism, growth and differentiation. In 2008, the Amsterdam Lysosome Center, Sphinx, was launched within the AMC. Already designated as a national centre for evaluation and treatment of LSDs, the innovative translational research in SPHINX involves participation in international clinical trials with new therapeutic agents (small compounds, plant-produced recombinant enzymes) and application of new treatment modalities (bone marrow transplantation, chaperone therapy). The laboratory for Genetic Metabolic Diseases at the AMC is well known for its combined diagnostic and research facilities with different sections for Metabolite, Enzyme and DNA analysis.
Scientific Organising Committee:
Jean-Marie Saudubray, Pitié Salpêtrière Hospital, Paris, France
Matthias Baumgartner, University Children’s Hospital, Zurich
Ron Wanders, Academic University Center, University of Amste
Course description
Almost40new diseases related to genetic defects in enzymes involved in the biosynthesis and remodelling of phospholipids, sphingolipidsand complex fatty acids have been described within the last 5 years. New descriptions and new phenotypes are expanding rapidly in paediatrics and adulthood. They involve central and peripheral nervous system,(upper and/or lower motoneuron degeneration,spastic paraplegia, neurodegeneration with brain iron accumulation), heart and muscle (myopathies,recurrent myoglobinuria), eye (retinitis pigmentosa), skin (Ichthyosis), bone (chondrodysplasias), liver, immune system, etc.
This course presents a first tentative overview of this new group of IEM and more broadly provides an update on other IEM involving complex lipids, namely very long chain fatty acids,plasmalogens, phosphatidylinositides,dolicholand glycolipids linked to congenital disorders of lipid glycosylation and dystroglycanopathies. Because of the implication of several cellular compartments, this new group of disorders affecting the synthesis and remodelling of complex molecules challenges our current classification of IEM still largely based on cellular organelles – i.e. mitochondrial, lysosomal, peroxisomal disorders. While most of these new disorders have been identified by next generation sequencing,this course emphasizes the promising role of lipidomics in deciphering their pathophysiology and identifying therapeutic targets.
Target audience: already trained metabolic physicians and clinical biochemists, geneticists, pediatric and adult neurologists and paediatricians.
Learning objectives
- To discover a new group of inherited metabolic diseases (IEM):the Inborn errors of the synthesis and remodeling of complex lipids.
- To learn the biochemical and clinical classification of these disorders: IEM of Glycerolipids (triglycerides),Glycero phospholipids, Ether phospholipids (plasmalogens),Phosphatidylinositides,Sphingolipids,Isoprenoids(oxysterols,dolichol,coenzyme Q),Glycolipids,Complex long chain and very long chain fatty acids and eicosanoids derived from arachidonic acid.
- To learn about the phosphatydyl inositol pathway and therelevance of the different related molecules in cell division, immunity,cancer and signaling.
- To study the synthesis of lipid linked oligosacharides (LLOs) and understand the significance of this complex molecule inglycosylation and how LLOs are used in diagnostics.
- To understand thebasis of dystroglycanopathies due to dolichol related defects, reviewthe links between different cell compartments and see how mannose linksthe different pathways to each other.
- To challenge the current classification of IEM based on cellular organelles.
- To learn the clinical presentations focusing on central and peripheral nervous system (many neurodegenerative disorders), muscular, orthopedic, skin, eye, inflammatory,visceral and multisystemic presentations.
- To diagnose these disorders using biochemical screening tests and molecular technics.
- To discover lipidomics, a new methodology able to identify > 1000 molecules in biological fluids (plasma, urine,CSF,cultured fibroblasts).
Participant profile:
This course is aimed atalready trained metabolic physicians and clinical biochemists; geneticists;paediatric and adult neurologists; paediatricians.
Fees
The standard course fee of 450€covers:
- 2 nights hotel accomodation including breakfast
- Lunch, coffee and dinner during the course
Participants are responsible for their own travel arrangements to and from the course.
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 13th May 2015.
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 15 days following the deadline for registration.
CME accreditation:
An application will be made for to the EACCME for CMEaccreditation.
Programme
Wednesday 24th
12-14.00Registration and snack lunch
14.00Introduction Goals of the course; IEM of complex lipids/FA synthesis disorders, an overview: Jean-Marie Saudubray (Paris)
14.30 Quiz
I Phospholipids
Chair: Matthias Baumgartner (Zurich) RonWevers (Nijmegen)
14.45Phospholipids synthesis:Overview
FoudilLamari(Paris)
15.15Lipid metabolism in the mitochondrial membrane
Johannes Mayr(Salzbourg)
15.45Metabolic defects in phospholipid metabolism I: Cardiolipin pathwayBarth,Megdel,Sengers syndromesSaskia B Wortmann (Nijmegen)
16.15Discussion
16.30Metabolic defects in phospholipid metabolism II:The phosphocholine,phosphatidyl serine pathway:Choline kinase, Phosphocholinecytidylyltransferase,Phosphatidylserine synthase 1
Sergio Sousa (Coimbra)
Discussion
17.00Coffee
17.30Membrane remodellingand phospholipids release I :Disorders with brain iron accumulation(PLA2G6,Fatty acid hydroxylase,PKAN,CoA synthase)
ValeriaTiranti(Milan)
18.00Membrane remodelling and phospholipids release II: Spastic paraplegias,ARCA and other neurodegenerative presentations(DDHD1,DDHD2,CYP2G6,NTE,PNPLA6,ABHD12)
Fanny Mochel (Paris)
18.30Discussion
18.45End of the session
19.30Dinner
Thursday 25th
II VLFCA, Plasmalogens, Sphingolipids
Chair:Marie Vanier (Lyon) Ron Wanders (Amsterdam)
8.30VLCFA and Branched chain fatty acids synthesis (including Racemase,Elongases,3 OH acyl CoA hydratase and FAR1..)
Ron Wanders (Amsterdam)
9.00Plasmalogen/ether phospholipids and fatty alcohol synthesis (including Sjogren Larsson) :
Pedro Brites(Porto)
9.30Discussion
9.40Sphingolipids synthesis (SPTLC1/ SPTLC2, GM2 and GD2 synthase,GM3 synthase,Ceramide synthase 2,FA2H..)
Thierry Levade(Toulouse)
10.10Consequences of SRT on sphingolipidsmetabolism : Frances Platt (Oxford)
10.40Discussion
10.50Coffee
Chair :Frances Platt (Oxford)
11.20Niemann Pick C (and other defects disturbing cholesterol trafficking)
Marie Vanier .
Discussion
11.50Palmitoylation /depalmitoylation:primary (like in CLN1) and secondary defects (like in neurodegenerative disorders)
Thorsten Hornemann(Zurich)
Discussion
12.20Lunch
III Triglycerides- Diagnostic approach
Chair:TBC
13.30Triglycerides synthesis and lipases:Lipin,DGAT I/II,ATGL,CGI 58 (ChanarinDorfmann) Perilipin,Berardinelli-Seipcongenitallipodystrophy.
Grant Mitchell (Montreal)
Discussion
Chair:Frederic Sedel (Paris), JaakJaeken (Leuwen)
14.00Overview of neurologic presentations
Angela Garcia (Barcelona)
14.30Overview of extra neurologicpresentations (muscle, immunologic,retinitis,visceral,)
Pascale Delonlay (Paris)
15.00Coffee
15.302.30hours parallel workshops with audience divided in 3 groups A,B,C:
Based on participants’ and workshop leaders’ case reports.
-A.Lipidomics
Chair: Frederic Vaz (Amsterdam), Benoit Colschand Christophe Junot(Orsay)
-B. Neurological presentations
Chair: Angela Garcia-Fanny Mochel
-C.Chondrodysplasia
Chair: Valerie Cormier(Paris)and Sergio Sousa(Coimbra) 1.15hrs
16.45Break
17.15Parallel workshops
A and B continued
C. Skin presentations
(TBC )
18.30End of session
19.30Dinner
Friday 26th
8.30hWorkshop reports (20-25 minutes for each presentation including discussion by leaders)
10.00Break
IV Glycolipids ,Dolichol ,GPI anchor and new related glycosylation defects
Chair :Eva Morava (New Orleans),Ron Wewers (Nijmegen)
10.30Lipid linked oligosaccharides and related defects
Christian Thiel (Heidelberg)
11.00Dolichol synthesis related defects I:recognizable clinical phenotypes
Eva Morava(New Orleans)
11.30Dolichol and the alpha-dystroglycanopathies:the DPM complex
(TBC)
12.00GPI anchor defects and syndromes of GPI anchor synthesis
JaakJaeken(Leuwen)
12.30Lunch
IV Phosphatidylinositol (PI) defects and towards new lipid defects
Chair:TBC
13.30Phosphatidylinositol defects, background and overview
Mark Waugh (London)
14.00Clinical phenotypes and novel defects of PI synthesis
MiskiMohamed (Nijmegen)
14.30Quiz & concluding remarks
15.00 End of course and departure