Overview

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.

Publications

FLDA genomic rearrangements cause periventricular nodular heterotopia.
Clara van Karnebeek
01/2012

Diagnostic analysis of the Rubinstein-Taybi syndrome; five cosmids should be used for microdeletion and a low number of protein truncating mutations.
Clara van Karnebeek

Further delineation of the chromosome 14q terminal deletion syndrome
DOI: 10.1002/ajmg.10207

The MorquioBetter Project: Global patient registry for Morquio syndrome type B disease and late-onset GM1-gangliosidosis
DOI: 10.1016/j.ymgme.2012.11.020

Treatable inborn errors of metabolism causing intellectual disability: A systematic literature review
DOI: 10.1016/j.ymgme.2011.11.191

Pyridoxine dependent epilepsy and antiquitin deficiency
DOI: 10.1016/j.ymgme.2011.05.014

Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness
DOI: 10.1038/sj.ejhg.5201279

The treatable intellectual disability APP www.treatable-id.org: A digital tool to enhance diagnosis & care for rare diseases
DOI: 10.1186/1750-1172-7-47

Expanding the clinical phenotype of the mitochondrial m.13513G>A mutation with the first report of a fatal neonatal presentation
DOI: 10.1111/j.1469-8749.2010.03907.x

Etiology of Mental Retardation in Children Referred to a Tertiary Care Center: A Prospective Study
DOI: 10.1352/0895-8017(2005)110[253:EOMRIC]2.0.CO;2

Lysine restricted diet for pyridoxine-dependent epilepsy: First evidence and future trials
DOI: 10.1016/j.ymgme.2012.09.006

An aetiological study of 25 mentally retarded adults with autism
DOI: 10.1136/jmg.39.3.205

Natural history of cardiovascular manifestations in Marfan syndrome
DOI: 10.1136/adc.84.2.129

Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience
DOI: 10.1136/jmg.39.8.546

Associations between chromosomal anomalies and congenital heart defects: A database search
DOI: 10.1002/(SICI)1096-8628(19990521)84:23.0.CO;2-5

Phenotypic abnormalities: Terminology and classification
DOI: 10.1002/ajmg.a.20249

Research

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)

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 been successful in more than 4 families … with more to come.

Grants

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

2015-2017: CAUSES Clinic,"Mining for Miracles," CoPI Jan Friedman, $2,500,000.

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

Honours & Awards

IG Maud Menten New Principal Investigator Finalist Prize (CIHR) – 2013

2014 MSFHR Scholar Award – 2014

Research Group Members

Lin-hua Zhang