Videos

Friday, May 20

Saturday, May 21

  • 0900-1100 | Morning Session 1: High Throughput Technologies for Personalized Management of Inborn Errors of Metabolism

  • 1115-1300 | Morning Session 2: Enhancement of Established Therapies


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    Friday, May 20, 0835-1000
    Morning Session 1: The National Working Group Experience

     

    Moderators:
    Pranesh Chakraborty, University of Ottawa
    Beth Potter, University of Ottawa

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Understand the strengths and limitations of observational research methods to inform care for inherited metabolic diseases (IMD).

    • Appreciate the types of analyses that are or will be possible using the Canadian Inherited Metabolic Diseases Research Network (CIMDRN) data to inform care for patients in Canada.

    • Understand approaches to improving patient care for IMD using patient reported outcomes.

    • Learn about the health system impacts of newborn screening for IMD.

    • Understand an approach to using multiple data sources to better understand the management of IMD and impact on outcomes.

    This session will focus on approaches to generating evidence to improve health care for children with inherited metabolic diseases. Presenters will describe research conducted by the Canadian Inherited Metabolic Diseases Research Network (CIMDRN), a pan-Canadian network and program that focuses on outcomes from across the “triple aim” of clinical endpoints, patient and family experiences, and health system impacts. We will also highlight the features of CIMDRN’s data infrastructure, identify opportunities for future analyses, and describe research conducted by CIMDRN trainees.

     

    0835-0840 Introduction

    Pranesh Chakraborty, University of Ottawa

     

    0840-0850 Synthesizing Evidence About Treatments for Rare Diseases

    Kylie Tingley, University of Ottawa

     

    0850-0915 A Canadian IMD Cohort: Clinical Description and Research Potential

    Pranesh Chakraborty, University of Ottawa
    Kylie Tingley, University of Ottawa

     

    0915-0930 The Health System Impact of Newborn Screening for IMD

    Sara Khangura, University of Ottawa

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Describe the epidemiology of MCADD and PKU in Ontario.

    • Compare health services utilization at a population-level between children affected with MCADD and PKU versus those unaffected.

    • Summarize the health systems impact of MCADD and PKU in a 7-year Ontario birth cohort.

    • Discuss future opportunities for health systems impact research in provinces other than Ontario.

    The long-term health system impact of IMDs is not well-understood. Using population-based newborn screening (NBS) and health care administrative data, we have described the epidemiology and health services utilization of Ontario children with MCADD and PKU in the first few years of life, and compared this to an unaffected cohort. The session will be of value to clinicians, policy makers, health services researchers and epidemiologists.

     

    0930-0950 Patient and Family Experiences with Health Care for IMD

    Beth Potter, University of Ottawa

     

    0950-1000 A Comprehensive Perspective on the Canadian Experience of Modern PKU Management

    Nataliya Yuskiv, University of British Columbia

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Discuss an approach to using multiple data sources to better understand the management of Phenylketonuria.

    • Discuss the comprehensive perspective on PKU management with relation to clinically important outcomes.

    • Compare surrogate biomarkers and clinically meaningful outcomes in PKU.

    “A Comprehensive Perspective on the Canadian Experience of Modern PKU Management” will outline the use of different databases in order to review current clinical and nutritional management practices in Canada. The presenter will talk about the importance of comprehensive comparison of nutritional and clinical PKU management practices and its comparison with the biomarker and clinically meaningful outcomes data. The latter are derived from CIMDRN database and patient-reported Quality of Life surveys. The ultimate objective of this project is to collect evidence that helps further optimization of the outcomes in children with PKU. The session will be of value to health care professionals who provide care to patients with PKU.

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    Friday May 20, 1030-1230
    Morning Session 2: Development of Treatments, Evidence and Policy

     

    1030-1100 Introduction/Overview: A 360 Degree Review on Rare Disease Drug Development

    Sylvia Stockler, BC Children’s Hospital

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Describe therapies for inborn errors of metabolism developed during the past centuries.

    • Discuss upcoming therapies such as gene repair therapies, bioengineered enzyme replacement therapies, chaperones and the microbiome as a therapeutic vehicle.

    • Describe challenges in creating evidence and demonstrating cost effectiveness of orphan drugs.

    • Describe the role of patients and families in orphan drug development.

    There has been an enormous progress in the development and marketing of therapies for rare inborn errors of metabolism during the last decades.
    Next generation enzyme replacement therapies enabling the transport of large molecules across the blood brain barrier, and gene repair approaches such as read through molecules and antisense oligonucleotides are being developed for numerous IEMs and neurometabolic conditions. Limited patient numbers and limited knowledge of the natural history of rare diseases pose challenges upon creation of high level evidence and demonstration of clinically meaningful outcomes. Active involvement of patients and families in the development of therapies promotes the development of drugs for ultrarare diseases.

     

    1100-1130 Development of Treatments, Evidence and Policy

    Martin Offringa, Hospital for Sick Children

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Explain what types of evidence are needed for what types of decisions.

    • Compare international approaches to generation of evidence in rare diseases.

    • Apply a roadmap for “evidence to decisions”.

    This presentation will examine what the evidence needs are for making informed decisions in the management of rare diseases. In the field of rare diseases specific solutions are needed to overcome challenges of gathering and knowledge translations evidence; these will be reviewed with an international perspective. The role of patient registries and de adoption of “standards of care” will be highlighted. The session would be of interest to scientists involved in the development of therapies as well as clinicians treating patients with rare diseases.

     

    1130-1200 Platform Presentations

     

    1200-1230 Assessment of Health Technologies and Value Based Decision Making

    Devidas Menon, University of Alberta

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Explain what “health technology assessment” means.

    • Compare the challenges of assessing treatments for rare diseases with those associated with common diseases.

    • Discuss the roles of values in resource allocation decision-making.

    This presentation will explain what health technology assessment (HTA) is, and its comprehensive scope. The specific challenges that HTA faces in the field of rare diseases will be described, and the importance of broadening the view of what “value” means will be discussed. This should be of interest to scientists involved in the development of therapies as well as physicians treating patients with rare diseases.

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    Friday May 20, 1330-1445
    Afternoon Session 1: Mitochondrial Disorders and Innovative Therapies 1

     

    1330-1345 MitoCanada

    Christopher Newell, University of Calgary

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Describe MitoCanada – who they are, what they do.

    • Describe the role patients’ organizations play in not only funding research but as partners and developers of research and their potential involvement in the regulatory process.

    • Discuss upcoming opportunities for clinicians, scientists and trainees to collaborate on a national agenda for mitochondrial disease.

    This brief presentation will provide highlights about MitoCanada, Canada’s only not-for-profit organization with a mission to transform the outlook for anyone facing a diagnosis of mitochondrial disease. MitoCanada aims to provide patients, their families and caregivers with knowledge/tools to improve their quality of life while raising public awareness of mitochondrial disease and advancing Canadian research activities. MitoCanada is positioning itself to play a leading role in creating a multi-stakeholder network that will be Canada’s authoritative voice on evidence-based approaches for improved care for mitochondrial disorders/dysfunction. The session will be of interest to clinicians, scientists and trainees wanting to participate in MitoCanada’s plans.

     

    1345-1400 Platform Presentation

     

    1400-1445 Treatment of Mitochondrial Disorders

    Mark Tarnopolsky, McMaster University

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Describe the cellular consequences of mitochondrial dysfunction.

    • Understand the efficacy behind the “mitochondrial cocktail”.

    • Describe the effects of exercise upon mitochondrial function.

    • Understand the potential for exosomes as therapeutic enablers for treatment of mitochondrial disease.

    Mitochondrial dysfunction leads to many potentially deleterious consequences including; oxidative stress, inflammasome activation, apoptosis, reduced aerobic energy supply, and depletion of alternative energy sources. The traditional therapeutic approaches to therapy has been a “mitochondrial cocktail” with components designed to mitigate oxidative stress (i.e., alpha- lipoic acid), bypass specific defects (i.e., coenzyme Q10), and provide alternative energy sources (i.e., creatine monohydrate). In addition, both endurance and resistance exercise have been show to confer clinical benefit to patients with mitochondrial cytopathies. We have recently shown that most of the systemic benefits of endurance exercise are mediated by the inter-organ exchange of exosomes. We have developed methods for extracting pure exosomes and loading them with therapeutic payloads (i.e., mRNA, siRNA, protein, tRNA, miRNA). We have used exosome-mRNA and exosome-protein approaches to effectively treat Pompe disease, Duchenne MD, NP-C and other genetic disorders.

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    Friday May 20, 1500-1730
    Afternoon Session 2: Innovative Therapies 2

     

    1500-1545 Cell Based Therapies for Metabolic Disorders

    Stephen Strom, Karolinska Institutet

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Understand that cell therapies exist for liver diseases.

    • Understand that cell therapies could be either mature liver cells or stem-like cells.

    • Understand the potential problems and benefits of cellular therapies.

    Our group has developed the technology needed for cellular therapy of liver disease. Our initial studies were concerned with the transplantation of mature liver cells (hepatocytes) into patients with liver disease. Recently we have expanded this cellular therapy to stem-like cells from the human amnion, which is part of the placenta. In our preclinical studies with human amnion epithelial cells, they correct 4 different metabolic liver diseases, as well as acute liver failure. We have received an ethical permit to transplant up to 10 patients with this new stem cell source.

     

    1545-1630 Treatment of the Hepatic Glycogen Storage Diseases

    David Weinstein, University of Florida

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Discuss treatment strategies for the glycogen storage diseases.

    • Compare the differences between treatment of GSD I and the ketotic forms of GSD.

    • Summarize the complications which can occur in the hepatic glycogen storage diseases.

    • Discuss why high protein is critical in GSD type III.

    • Explain why all types of GSD are now restricting carbohydrate.

    • Discuss why fructose, sucrose, and galatose require restriction in GSD I.

    The prognosis for people born with the glycogen storage diseases has markedly improved. There is increasing evidence that all complications in the hepatic forms of GSD are preventable with optimal management. This talk will summarize changes in treatment for the hepatic glycogen storage diseases with an emphasis on differences between GSD I and the ketotic forms of GSD. The session will be of values to metabolic physicians, geneticists, endocrinologists, pediatricians, medical biochemists, specialists involved with GSD patients, nurses, dietitians, and anyone involved with seeing patients with glycogen storage disease.

     

    1630-1730 Updates and Evidence: Management and Treatment of Urea Cycle Disorders

    Andreas Schulze, Hospital for Sick Children

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Explain the goals of management of patients with urea cycle defects.

    • List specific treatments in urea cycle defects.

    • Discuss limitations of current treatments.

    • Summarize new trends in management and treatment of urea cycle defects.

    • Discuss outcomes of Rare Disease Networks on the example of the Urea Cycle Disorder Consortium.

    This presentation will inform about new findings and trends in the management and treatment of patients with Urea Cycle Disorders. This session will be of value to: metabolic physicians, pediatricians, allied health professionals, geneticists, laboratory specialists and scientist working in the field of Inborn Errors of Metabolism.

     

    Aneal Khan, University of Calgary, Alberta Children’s Hospital

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Describe the role of liver cell transplant for management of urea cycle diseases.

    • Describe a novel technique using cell free DNA to look for engraftment of liver cells.

    • Discuss principles of hemodialysis in managing patients with difficult to treat hyperammonemia.

    This session will review the international experience with using liver cell transplants as bridge therapy for urea cycle diseases, assessing for engraftment using a novel non-invasive cell free DNA method and principles of hemodialysis in managing hyperammonemia.

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    Saturday May 21, 0900-1100
    Morning Session 1: High Throughput Technologies for Personalized Management of Inborn Errors of Metabolism

     

    Moderators:

    Christiane Auray-Blais, Université de Sherbrooke

    John Mitchell, Montreal Children’s Hospital

     

    0900-0930 Genomics to Diagnose Neurometabolic Disease: Bigger Always Better?

    Clara van Karnebeek, BC Children’s Hospital/University of British Columbia

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Summarize the CCMG 2015 position on clinical indications for exome sequencing.

    • Discuss the framework for interpretation of variants accordng to the ACMG criteria for variant pathogenicity.

    • Discuss the advanges of the metabolic phenotype for variant prioritization and subsequent validation of causality.

    • Discuss the results of the TIDEX neurometabolic gene discovery study.

    • Discuss the use genomics as 1st line test in the biochemical genetics clinic.

    Genomics has revolutionized our ability to diagnose and uncover rare conditions. In this presentation, the strengths and limitations of whole exome / genome sequencing specifically in relation to inborn errors of metabolism will be discussed. The CCMG 2015 position statement on the application of this technology in the clinical setting as well as the available tools and ACMG criteria for variant interpretation and validation will be summarized. Our Tidex discovery study applying combined -omics technology will be used as illustration of the advantages of the metabolic phenotype for gene discovery and the potential impact on management. Finally, the question of whether the ‘exome or genome as 1st line test’ in the biochemical genetics clinic makes sense will be considered.

     

    0930-1000 Expanding Screening and Diagnostic Capacity for Amino Acidurias Through Tandem Mass Spectrometry

    Graham Sinclair, BC Children’s Hospital/University of British Columbia

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Summarize the capacity constraints of traditional amino acid analysis.

    • Discuss the benefits and drawbacks of transitioning amino acid analysis to tandem mass spectrometry.

    • Explore the role for bloodspot amino acid analysis in routine and acute metabolic monitoring.

    This presentation will discuss the capacity bottleneck we faced with traditional amino acid analysis and outline our transition to tandem mass spectrometry. We will explore the impact that this has on both routine testing and acute monitoring during metabolic crisis. Finally, we will discuss the role for bloodspot analyses in patient monitoring and the factors to be considered in such an approach. This session will be of value to both laboratory and clinical biochemical geneticists and others caring for metabolic disease patients.

     

    1000-1030 New Twists on Old Biomarkers

    Paula Waters, Centre hospitalier universitaire de Sherbrooke (CHUS)

     

    Learning Objectives: At the end of this session, participants will be able to:

    • List three examples in which infants with elevation of a ‘classic disease biomarker’ were subsequently found to have a distinctly different biochemical condition.

    • Contrast ‘Combined malonic and methylmalonic aciduria’ with other forms of methylmalonic aciduria.

    • Identify a potential cause of hypersuccinylacetonemia other than tyrosinemia type 1.

    • Consider one more potential cause in the differential diagnosis of orotic aciduria.

    This presentation focusses not on ‘high throughput technologies’ per se, but rather on the next steps which follow first-line screening; particularly the process of refining the differential diagnosis. I will describe three examples from the experience of our Biochemical Genetics Laboratory, in which the final diagnosis was something other than the intended disease target of the primary screening, with quite different clinical implications.

     

    1030-1100 Mass Spectrometry Biomarker Analysis for the Identification, Monitoring and Follow-up of Patients

    Christiane Auray-Blais, Université de Sherbrooke

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Distinguish different mass spectrometry methods for biomarker analysis.

    • Interpret mass spectrometry results for detection of patients.

    • Assess the importance of robust technologies for monitoring treated patients.

    This lecture will focus on biomarker discovery for Fabry disease using a metabolomic approach, method development of targeted biomarkers for patients with cardiac variant mutations, and a novel mass spectrometry multiplex methodology for glycosaminoglycan quantitation for different types of mucopolysaccharidoses. A second-tier method for keratan sulfate analysis for Morquio IVA patients will also be presented. The session will be of value to: geneticists, pediatricians, nephrologists, cardiologists, medical biochemists, researchers (Ph.D. and master’s degree students), genetic counsellors, nurses, etc.

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    Saturday May 21, 1115-1300
    Morning Session 2: Enhancement of Established Therapies

     

    1115-1145 European Dietary Guidelines of Propionic Acidaemia (PA) and Methylmalonic Aciduria (MMA)

    Anita MacDonald, Birmingham Childrens Hospital

     

    Learning Objectives: At the end of this session, participants will be able to:

    • Understand the different approaches to the nutritional support of PA and MMA across Europe.

    • Gain insight into the European energy and protein requirement guidelines for MMA/PA.

    • Understand the European approach to nutritional support/enteral feeding in MMA/PA.

    • Gain insight into the application of dietary emergency regimens across Europe.

    Children with methyl malonic aciduria (MMA) and propionic aciduria (PA) are dependent on complex dietary treatments. Historically, some of the existing dietary practices (e.g. use of precursor-free amino acids) have developed from the dietary management of amino acid disorders such as phenylketonuria (PKU). The E-IMD European (Baumgartner et al 2014) guidelines on methyl malonic aciduria and propionic aciduria have tried to address many controversial aspects of dietary treatment, including the severity of protein restriction, use of supplementary precursor-free L-amino acids, energy requirements, and role of enteral feeding. However, it is difficult to agree definite guidelines when so little research has been conducted about its nutritional management. The European guidelines suggest that dietary management should be based on adequate energy supply combined with avoidance of prolonged fasting and reduced intake of precursor amino acids through a restricted natural protein diet. They advocate that protein tolerance should be titrated individually, with the FAO/WHO/UNU (2007) safe levels of protein intake providing a useful guide for protein prescription. Precursor-free L-amino acids should only be used to supplement natural protein intake if intake is below safe levels of protein intake.

    What is known about European dietary practices? Large European surveys on dietary management of MMA and PA indicate that dietitians have widely different practices for the prescription of substrate-free amino acids and natural protein restriction. Many but not all centres provide additional precursor-free amino acids (in varying amounts) to supplement natural protein intake. The amount prescribed in cross sectional and cohort studies varies between 15-50% of total protein intake, partly influenced by metabolic stability, natural protein intake tolerated, patient age, disorder severity and local practice. The long term effect of precursor-free amino acids requires further research to delineate their benefit. There is little evidence to suggest they improve metabolic control or long term outcome; and they may be mainly broken down and excreted as urea, and are associated with deficiencies of valine and isoleucine.

    What is unknown about European dietary practices? Little is known about quality of natural protein sources given for natural protein intake, use and composition of enteral feeds, quality of diets (particularly intake of fibre, micronutrients, and quality of fatty acids), and policies on hydration. Overall, these are areas that are given inadequate attention in MMA and PA. Although each of these areas were discussed in the European guidelines, it was difficult to give definite guidelines and any recommendations were based on consensus only.

    It is clear that multi-centre research is necessary to address many of the important nutritional management issues that remain in MMA and PA. Until this is done, there will continue to be much ongoing debate.

    The session will be of value to: medical doctors, nurses and dietitians.

     

    1145-1215 Dietary Management of Tyrosinemia

    Manon Bouchard, CHU Sainte-Justine

     

    Learning Objectives: At the end of this session, participants will be able to:

    • List the main elements of nutritional treatment of tyrosinemia type 1.

    • Recognize how the nutritional managment must be adjusted with age.

    • Identify the nutritional challenges that arise in maintaining optimal nutritional status in all age groups.

    This lecture will summarize the nutritional treatment of tyrosinemia type 1 at different ages. Because low phenylalanine plus tyrosine diet is prescribed throughout the patient’s life, nutritional treatment must be adjusted and individualized. Our current treatment approach will be discussed and will include case histories of challenging patients that we have encountered.

     

    1215-1245 Platform Presentations

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