• van Karnebeek, Clara


    Associate Clinician Scientist, CFRI
    Associate Member, Centre for Molecular Medicine and Therapeutics
    Clinical Assistant Professor, Division of Biochemical Diseases, Department of Pediatrics, Faculty of Medicine, UBC

    Degrees / Designations
    MD, PhD
    Primary Area of Research
    Centre for Molecular Medicine & Therapeutics
    Developmental Neurosciences & Child Health
    Secondary Area(s) of Research
    604-875-2345 ext. 5500
    Lab Phone
    604-875-2345 ext. 5500
    Mailing Address
    BC’s Children’s Hospital

    Biochemical Diseases Clinic
    Rm K3-201, 4480 Oak Street
    Vancouver, BC  V6H 3V4

    Affiliate Websites
    Research Areas
    Intellectual disability, global developmental delay, genetic etiology, inborn errors of methodology, next-generation sequencing, treatment, knowledge translation, APPs.

    As a pediatrician and biochemical geneticist, working 60% clinically, my research focuses on preventing and treating rare genetic diseases causing intellectual disability or neurodevelopmental impairments. 

    With our project TIDE-BC (www.tidebc.org) we are shifting the approach to cognitive impairments, which affect 2-3% of the population worldwide and often is accompanied by behavioral and organ abnormalities, from descriptive to interventional. Rare metabolic diseases are amenable to treatments such as medication, diets, supplements, and if diagnosed early enough, can prevent or limit brain damage. Our collaborative team is working with specialists in BCCH and across BC to screen for these diseases in each child with developmental delays, using laboratory and digital technologies such as the APP www.treatable-id.org.  

    Gene and disease discovery is another exciting aspect of our TIDE research, and the number of treatable diseases is increasing from 81 to 82 and more. Understanding diseases better also allows for new treatments, such as a recently developed diet for a metabolic epilepsy. To make full circle we have to test the effectiveness and safety of such treatments, and we do this using new trial methodologies … and make sure the new knowledge reaches the patient from bench to bedside to benefit children in B.C. and beyond. 

    Current Projects

    Treatable Intellectual Disability Endeavor in British Columbia: (TIDE-BC, www.tidebc.org). Role: co-founder & lead clinician scientist. With the funding obtained via the highly competitive Collaborative Area of Innovation grant (BC Children’s Hospital Foundation, Vancouver CA) of $2.25 million dollars, we currently are implementing the diagnostic TIDE protocol in the province of British Columbia to enhance early diagnosis of treatable inborn errors of metabolism. In the first year 5% of ID patients were found to suffer a disease we can treat to prevent brain damage and help them achieve optimal function. Our goal is to produce leading edge knowledge in the field of rare diseases and measurable improvements in child health through personalized medicine. Dr Stockler-Ipsiroglu and I coordinate the roles and input of a collaborative team of more than 30 scientists and clinicians. One of our most exciting projects within TIDE is the collaborative whole exome sequencing to discover new treatable intellectual disabilities; so far we have bene successful in more than 4 families … with more to come.

    Collaborative Research in Pyridoxine Dependent Epilepsy, a rare metabolic epilepsy. Role: clinical researcher & organizer of the 2010 Vancouver Workshop and the 2011 / 2012 International Workshop to set up an international trial for ‘Lysine restriction in Pyridoxine Dependent Epilepsy’ with implementation of novel trial methodologies (project leader: Sylvia Stockler-Ipsiroglu, MD PhD). We have published the 1st study on the results of a new treatment for PDE, the lysine restricted diet and are now developing a worldwide study to produce more solid evidence for the effectiveness of this approach (www.pde-online.org)

    Creation and design of the website www.TreatableID.org with Apps for handheld devices, based on our Systematic review on Treatable Metabolic Disorders causing Intellectual Disability.  Performed in BC Children’s Hospital, University of British Columbia (Vancouver, CA) during the period 2009-2011 in collaboration with Sylvia Stockler-Ipsiroglu, MD PhD (neurometabolic specialist, principal applicant on this grant). Our evidence-based approach to rare diseases, i.e. the identification of treatable inborn errors of metabolism presenting with intellectual disability and grading the levels of evidence for therapeutic effect, is an innovation in this field. This Knowledge Translation & Transfer activity via modern-day digital tools with rigorous evaluation, has the potential to reach the all clinicians confronted with the challenging task to identify / rule out a treatable case in their ID patients. This App was published recently in the Orphanet Journal of Rare Diseases and has won numerous prizes. This activity lies at the basis of TIDE-BC.

    Selected Publications

    van Karnebeek CDM, Editorial:  Update on Research in Autism.  Scientific Journal on Autism (Wetenschappelijk Tijdschrijft Autisme) 2005 – 2009 (Published 3x a year).

    van Karnebeek C, Waters P, Sargent MA, Mezey MM, Wong LJ, Wang J, Stöckler-Ipsiroglu S. Expanding the clinical phenotype of the mitochondrial m.13513G>A mutation with the first report of a fatal neonatal presentation. Dev Med Child Neurol. 2011 Jun;53(6):565-568. doi: 10.1111/j.1469-8749.2010.03907.x. Epub 2011 Apr 19. 

    van Karnebeek CDM, Waters PW, Sargent MA, Mezei MM, Wong LJ, Wang J, Stockler-Ipsiroglu S.  Expanding the clinical phenotype of the mitochondrial M.13513G>A mutation with the first report of a fatal neonatal presentation. Dev Med Child Neurol 2011 Jun; 53 (6):565-8.

    Stockler-Ipsiroglu, Clayton P, Connolly M, Coulter-Mackie M, Gospe S, Mahmutoglu S, van Karnebeek C, et al.  Mini Review: Pyridoxine dependant epilepsy and antiqutin Deficiency.  Mol Genet Metab 2011;104:48-60.

    Clapham KR, Tu TW, Ganesh VS, Barry B, Chan Y, Mei D, Parrrini E, Funalot B, Dupuis L, Nezarati MM, du Souich C, van Karnebeek C, Guerrini R, Walsh CA.  FLNA genomic rearrangements cause periventricular nodular heterotopia.  Neurology 2012 Jan 24; 78(4):269-78.  Epub 2012 Jan 11.

    van Karnebeek CD, Stockler S.  Treatable inborn errors of metabolism causing intellectual disability: a systematic literature review.  Mol Genet Metab 2012 Mar;105(3):368-81. (Epub ahead of print).

    Stockler S, van Karnebeek C, Hartmann H, Jaggumantri S, Bok L, Cheng B, Connolly M, Coughlin C, Das A, Gospe S, Jakobs C, van der Lee H, Mercimek-Mahmutoglu S, Meyer U, Struyst E, Sinclair G, Van Hove J, Collet JP, Plecko B.  Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence & future trials.  Molecular Genetics and Metabolism, in press, July 2012.

    van Karnebeek C, Houben R, Lafek M, Giannasi W, Stockler S.  The treatable intellectual disability APP www.treatable-id.org: a digital tool to enhance diagnosis and care for rare diseases.  Orphanet Journal of Rare Diseases. 2012, 7:47.


    2010-2011: BC Clinical Genomics Network: High throughput sequencing for treatable inborn errors of metabolism causing intellectual disability and epilepsy. A pilot study, $25,000.

    2010-2011: Foundation Metakids, Netherlands, Development of evidence-based diagnostic protocol & digital tools for treatable intellectual disability, $35,000.

    2010-2011: Collaborative Area of Innovation BC Children’s Hospital Project (www.tidebc.org)“: Treatable Intellectual Disability Endeavor in BC. Project Development Grant, $25,000.

    2011-2012: Bluma Tischler Postgraduate Fellowship Award, UBC. Detecting pyridoxine dependent epilepsies in neonates and infants: a treatable cause of medically refractory epilepsy and intellectual impairment, $20,400.

    2011-2016: Collaborative Area of Innovation, B.C.’s Children’s Hospital. “Treatable Intellectual Disability Endeavor in B.C. (TIDE-BC)." $2.25 million.

    2012: The Canadian Society for MPS & Related Diseases “Morquio Better Project”, $50,000. 

    2013-2018: CIHR Operating Grant - "Expanding the number of treatable intellectual disabilities through an integrated "-omics" approach," $772,999.

    Honours & Awards

    Jan 2003: Most Outstanding Autism Research Distinction – awarded by the Dutch Scientific Journal for Autism.

    Jan 2011:  Laura McRae Award for Excellence in Pediatrics, UBC./BC College of Physicians and Surgeons, Pediatrics, ($1,200).

    Sept 2011 – Sept 2012: Bluma Tischler Fellowship Research Award, UBC, Research on Mental Retardation ($20,400).

    Third-Prize Winner as voted by peers for invited presentation (and Demo of TIDE app): “A revolutionary medical app that helps children with intellectual disabilities reach their full potential”. Interface Fall 2012.  Digital Health Innovation Summit, Vancouver, BC, Oct 16-18, 2012.  

    September 2013: Finalist, CIHR Institute of Genetics Maud Menten New Principal Investigator Prize (Clinical Theme)

    Research Group Members
    Sravan Jaggrawantu

    Marion Thomas
    Mir Lafek
    Michelle Higginson
    Casper Shyr
    Maria Boldut
    Tyler Murphy