• van Karnebeek, Clara


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

    Degrees / Designations
    MD, PhD, FCCMG
    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 Children’s Hospital

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

    Affiliate Websites
    Research Areas
    • Discovery of novel gene defects via integrated genomics and metabolomics
    • Treatable inborn errors of metabolism causing intellectual disability and epilepsy
    • Clinical and digital tools for the prevention, enhanced diagnosis and treatment of intellectual disability

    Early recognition of rare but treatable genetic diseases in children is the key to preventing certain forms of intellectual disability.

    “Intellectual disabilities are no longer necessarily an unchangeable fate,” says Dr. van Karnebeek. “Today, new tools allow us to diagnose and treat specific genetic conditions causing developmental delay and intellectual disability, previously thought to be permanent.”

    Dr. van Karnebeek’s research is aimed at discovering new inborn errors of metabolism, a class of genetic diseases that is particularly amenable to treatment. Her team uses a multidisciplinary approach involving the study of three “-omics” in patients: phenomics, their physical and biochemical properties, genomics, their genetic information, and metabolomics, their metabolite profiles. She established two large collaborative efforts, the Treatable Intellectual Disability Endeavor in BC (TIDEBC.org with Sylvia Stockler), and the international Omics2TreatID (omics2treatid.org), aimed at harnessing these new technologies for the discovery of genetic defects in children who present with intellectual disabilities and providing clinicians the tools for early recognition and management.

    Dr. van Karnebeek and her team already successfully identified a number of these defects, developed new treatments and were able to enhance identification of these diseases in BC Children’s Hospital. Over the past 2 years, 400 children with intellectual disability were systematically screened and 5% were identified to have treatable condition; treatment in these cases improved behavior, cognition and often changed the lives of the whole family.

    These diagnostic tools – a protocol supported by the Treatable-ID.org App - are now used by physicians around the world, allowing them to recognize diseases in newborns and treat these vulnerable patients before they suffer important brain damage.

    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 C, Murphy T, Giannasi W, Thomas M, Connolly M, Stockler-Ipsiroglu S. Diagnostic value of a multidisciplinary clinic for intellectual disability. Can J Neurol Sci. 2014 May;41(3):333-45. 

    van Karnebeek CD, Stockler-Ipsiroglu S, Jaggumantri S, Assmann B, Baxter P, Buhas D, Bok LA, Cheng B, Coughlin CR 2nd, Das AM, Giezen A, Al-Hertani W, Ho G, Meyer U, Mills P, Plecko B, Struys E, Ueda K, Albersen M, Verhoeven N, Gospe SM Jr, Gallagher RC, Van Hove JK, Hartmann H. Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The PDE Consortium Consensus Recommendations. JIMD Rep. 2014 Apr 19. [Epub ahead of print]

    “UBC scientist helps physicians diagnose a life-threatening disease in newborns”, Feature by UBC Faculty of Medicine, February 14, 2014. http://www.med.ubc.ca/ubc-scientist-helps-physicians-diagnose-a-life-threatening-disease-in-newborns/

    Michelle K Demos, Clara DM van Karnebeek, Colin JD Ross, Shelin Adam, Yaoqing Shen, Shing Hei Zhan, Casper Shyr, Gabriella Horvath, Mohnish Suri, Alan Fryer, Steven JM Jones and Jan M Friedman. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet Journal of Rare Diseases 2014, 9:15 doi:10.1186/1750-1172-9-15

    van Karnebeek CD, Sly WS, Ross CJ, Salvarinova R, Yaplito-Lee J, Santra S, Shyr C, Horvath GA, Eydoux P, Lehman AM, Bernard V, Newlove T, Ukpeh H, Chakrapani A, Preece MA, Ball S, Pitt J, Vallance HD, Coulter-Mackie M, Nguyen H, Zhang LH, Bhavsar AP, Sinclair G, Waheed A, Wasserman WW, Stockler S. Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood. Am J Hum Genet 2014 (ePub ahead of print).

    van Karnebeek, CDM, Shevell M, Zschocke J, Moeschler JB, Stockler S. The metabolic evaluation of the child with an intellectual developmental disorder: Diagnostic algorithm for identification of treatable causes and new digital resource. Mol Genet Metab 2014 (ePub ahead of print).

    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.

    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.

    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, Stockler S. Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence & future trials. Mol Genet Metab 2012 Nov;107(3):335-44.


    2013-2015: Genome BC: Synergizing -omics to discover treatable intellectual disabilities.

    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
    • 2014 MSFHR Scholar Award – 2014
    • IG Maud Menten New Principal Investigator Finalist Prize (CIHR) – 2013
    • Digital Health Innovation Summit Award – 2012
    • Bluma Tischler Fellowship Research Award – 2011
    • Laura McRae Award for Excellence in Pediatrics – 2011
    Research Group Members
    Sravan Jaggrawantu

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