Overview

I am a new staff member in Biochemical Diseases and was recruited on Sept 1st 2019. I was previously in Montreal, at CHU Sainte-Justine - Medical Geneticist, Medical Genetics Division, Department of Pediatrics and Biochemical Genetics Diagnostic Laboratory - Clinical Associate Professor, University of Montreal.

I worked as a medical geneticist, doing clinical and diagnostic lab work and research and have a specific expertise in inborn errors of metabolism, and the field of energy metabolism, mitochondrial diseases for which I have developed a multidisciplinary clinic in Montreal where we saw multiple patients with mitochondrial diseases. In parallel to the establishment of mitochondrial DNA sequencing and whole exome sequencing in the Molecular diagnostic laboratory and Genome Centre at CHU Sainte-Justine, I have established the functional diagnostic analysis in the biochemical genetics diagnostic laboratory : Blue Native PAGE and OXPHOS enzymatic activities on muscle fresh and frozen and fibroblasts to help improve the diagnostic yield of these conditions. I was the co-director of the biochemical genetics diagnostic laboratory and the director of the mitochondrial and lysosomal sectors of the lab. I was also part of the provincial multidisciplinary committee for enzyme replacement therapy for Gaucher disease.

Now, at BCCH, UBC, in the biochemical diseases division, with my colleagues, we want to explore further the treatment area of the mitochondrial and energy metabolism diseases field to improve patient's care. The diagnostic yield of these diseases has improved but further research needs to be done to develop the treatment and management aspects of these diseases to help reduce the mortality and morbidity and improve their quality of life. We have set up a new metabolic myopathies multidisciplinary clinic at BCCH. I will continue my collaboration on the RNA seq project and BCCH is being added as another center for the RNA sequencing ongoing project: RNA sequencing of undiagnosed myopathies with inconclusive WES and mitochondrial DNA sequencing, CHU Sainte-Justine, University of Montreal to continue improving our diagnostic yield.

In parallel, we have recently applied for funding to BCCHR for a new project: we would like to propose a platform for the in vivo assessment of therapies for metabolic myopathies from diet, to exercise therapy to various medications and in the future for new therapeutic agents and for gene therapy by collaborating with Rajavel Elango using various biomarkers and stable isotope related to the energy system capacity and collaborating with the Heart Center and the exercise physiology lab of the Heart's Center. The metabolic myopathies we will focus on consist on the phosphorylation oxidative defects (mitochondrial myopathies), fatty acid oxidation defects and muscle glycolysis defects (mcArdle). We propose, using stable isotope at rest and in a standardized exercise setting to evaluate patient's in vivo response to treatments. The platform will not only enable us to created individualized plans tailored to patient's needs: diet, appropriate exercises programs and the benefits of existing therapeutic agents, but it could help in the evaluation of innovative pharmalogical and gene therapies in the future by enabling us to develop new biomarkers to follow the response to therapies. It will also help us develop specific exercise plans to enable these children to remain physically active, avoiding deconditioning and the risk of a energy crisis. This will complement our Canadian expertise in the field of energy metabolism.

Publications

Evaluation of the quality of clinical data collection for a pan-Canadian cohort of children affected by inherited metabolic diseases: lessons learned from the Canadian Inherited Metabolic Diseases Research Network.
Orphanet journal of rare diseases
Tingley K and Lamoureux M and Pugliese M and Geraghty MT and Kronick JB and Potter BK and Coyle D and Wilson K and Kowalski M and Austin V and Brunel-Guitton C and Buhas D and Chan AKJ and Canadian Inherited Metabolic Diseases Research Network
DOI: 10.1186/s13023-020-01358-z
PubMed: 32276663
04/2020

Health Care for Mitochondrial Disorders in Canada: A Survey of Physicians.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
Paik K and Lines MA and Chakraborty P and Khangura SD and Latocki M and Al-Hertani W and Brunel-Guitton C and Khan A and Penny B and Rockman-Greenberg C and Rupar CA and Canadian Inherited Metabolic Diseases Research Network
DOI: 10.1017/cjn.2019.240
PubMed: 31387656
11/2019

Fulminant Necrotizing Enterocolitis and Multiple Organ Dysfunction in a Toddler with Mitochondrial DNA Depletion Syndrome-13
Journal of Pediatric Intensive Care
Nicolas Nardi and François Proulx and Catherine Brunel-Guiton and Luc L. Oligny and Nelson Piché and Grant A. Mitchell and Jean Sébastien Joyal
DOI: 10.1055/s-0039-1697620
10/2019

Muscle problems in juvenile-onset acid maltase deficiency (Pompe disease).
Paediatrics & child health
Zapata-Aldana E and McMillan HJ and Rupar T and Brunel-Guitton C and Chakraborty P and Mitchell JJ and Roth J and Tarnopolsky MA and Turner L and Campbell C
DOI: 10.1093/pch/pxy153
PubMed: 31239817
05/2019

Congenital lactic acidosis, cerebral cysts and pulmonary hypertension in an infant with FOXRED1 related complex 1 deficiency.
Molecular genetics and metabolism reports
Apatean D and Rakic B and Brunel-Guitton C and Hendson G and Bai R and Sargent MA and Lavoie PM and Patel M and Stockler-Ipsiroglu S
DOI: 10.1016/j.ymgmr.2019.100472
PubMed: 31065540
04/2019

Congenital lactic acidosis, cerebral cysts and pulmonary hypertension in an infant with FOXRED1 related complex I deficiency.
Molecular genetics and metabolism reports
Apatean D and Rakic B and Brunel-Guitton C and Hendson G and Bai R and Sargent MA and Lavoie PM and Patel M and Stockler-Ipsiroglu S
DOI: 10.1016/j.ymgmr.2018.12.006
PubMed: 30723688
01/2019

Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort.
Journal of inherited metabolic disease
Levtova A and Waters PJ and Buhas D and Lévesque S and Auray-Blais C and Clarke JTR and Laframboise R and Maranda B and Mitchell GA and Brunel-Guitton C and Braverman NE
DOI: 10.1002/jimd.12032
PubMed: 30740739
01/2019

Acute pediatric hyperammonemia: current diagnosis and management strategies.
Hepatic medicine : evidence and research
Savy N and Brossier D and Brunel-Guitton C and Ducharme-Crevier L and Du Pont-Thibodeau G and Jouvet P
DOI: 10.2147/HMER.S140711
PubMed: 30254497
09/2018

Acute pediatric hyperammonemia: current diagnosis and management strategies
Hepatic Medicine: Evidence and Research
Nadia Savy and David Brossier and Catherine Brunel-Guitton and Laurence Ducharme-Crevier and Geneviève Du Pont-Thibodeau and Philippe Jouvet
DOI: 10.2147/hmer.s140711
09/2018

Recessive mutations in NDUFA2 cause mitochondrial leukoencephalopathy
Clinical Genetics
Perrier, S. and Gauquelin, L. and T{\'e}treault, M. and Tran, L.T. and Webb, N. and Srour, M. and Mitchell, J.J. and Brunel-Guitton, C. and Majewski, J. and Long, V. and Keller, S. and Gambello, M.J. and Simons, C. and Vanderver, A. and Bernard, G.
DOI: 10.1111/cge.13126
2018

Combined malonic and methylmalonic aciduria due to ACSF3 mutations: benign clinical course in an unselected cohort
Journal of Inherited Metabolic Disease
Levtova, A. and Waters, P.J. and Buhas, D. and L{\'e}vesque, S. and Auray-Blais, C. and Clarke, J.T.R. and Laframboise, R. and Maranda, B. and Mitchell, G.A. and Brunel-Guitton, C. and Braverman, N.E.
DOI: 10.1007/s10545-018-0197-9
2018

Glutaric aciduria type 3: Three unrelated canadian cases, with different routes of ascertainment
JIMD Reports
Waters, P.J. and Kitzler, T.M. and Feigenbaum, A. and Geraghty, M.T. and Al-Dirbashi, O. and Bherer, P. and Auray-Blais, C. and Gravel, S. and McIntosh, N. and Siriwardena, K. and Trakadis, Y. and Brunel-Guitton, C. and Al-Hertani, W.
DOI: 10.1007/8904_2017_49
2018

Response to Newman et al.
Genetics in medicine : official journal of the American College of Medical Genetics
Parikh S and Goldstein A and Karaa A and Koenig MK and Anselm I and Brunel-Guitton C and Christodoulou J and Cohen BH and Dimmock D and Enns GM and Falk MJ and Feigenbaum A and Frye RE and Chinnery PF
DOI: 10.1038/gim.2017.164
PubMed: 29215644
10/2017

Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society.
Genetics in medicine : official journal of the American College of Medical Genetics
Parikh S and Goldstein A and Karaa A and Koenig MK and Anselm I and Brunel-Guitton C and Christodoulou J and Cohen BH and Dimmock D and Enns GM and Falk MJ and Feigenbaum A and Frye RE and Chinnery PF
DOI: 10.1038/gim.2017.107
PubMed: 28749475
07/2017

Reply.
The Journal of pediatrics
Ghaddhab C and Morin C and Brunel-Guitton C and Mitchell GA and Van Vliet G and Huot C
DOI: 10.1016/j.jpeds.2017.04.067
PubMed: 28550952
05/2017

Atypical juvenile presentation of GM2 gangliosidosis AB in a patient compound-heterozygote for c.259G > T and c.164C > T mutations in the GM2A gene.
Molecular genetics and metabolism reports
Martins C and Brunel-Guitton C and Lortie A and Gauvin F and Morales CR and Mitchell GA and Pshezhetsky AV
DOI: 10.1016/j.ymgmr.2017.01.017
PubMed: 28417072
04/2017

Premature Ovarian Failure in French Canadian Leigh Syndrome.
The Journal of pediatrics
Ghaddhab C and Morin C and Brunel-Guitton C and Mitchell GA and Van Vliet G and Huot C
DOI: 10.1016/j.jpeds.2017.02.008
PubMed: 28284481
03/2017

The Québec NTBC Study.
Advances in experimental medicine and biology
Québec NTBC Study Group and Alvarez F and Atkinson S and Bouchard M and Brunel-Guitton C and Buhas D and Bussières JF and Dubois J and Fenyves D and Goodyer P and Gosselin M and Turcotte JF
DOI: 10.1007/978-3-319-55780-9_17
PubMed: 28755196
01/2017

Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency
Journal of Medical Genetics
Yang, H. and Al-Hertani, W. and Cyr, D. and Laframboise, R. and Parizeault, G. and Wang, S.P. and Rossignol, F. and Berthier, M.-T. and Gigu{\`e}re, Y. and Waters, P.J. and Mitchell, G.A. and Alvarez, F. and Brunel-Guitton, C. and Buhas, D. and Dubois, J. and Gosselin, M. and Halac, U. and Maranda, B. and Mitchell, J. and Turcotte, J.-F.
DOI: 10.1136/jmedgenet-2016-104289
2017

A highly diverse portrait: Heterogeneity of neuropsychological profiles in cblc defect
JIMD Reports
Bellerose, J. and Neugnot-Cerioli, M. and B{\'e}dard, K. and Brunel-Guitton, C. and Mitchell, G.A. and Ospina, L.H. and Beauchamp, M.H.
DOI: 10.1007/8904_2015_517
2016

Biosynthesis of glycosaminoglycans: associated disorders and biochemical tests
Journal of Inherited Metabolic Disease
Sasarman, F. and Maftei, C. and Campeau, P.M. and Brunel-Guitton, C. and Mitchell, G.A. and Allard, P.
DOI: 10.1007/s10545-015-9903-z
2016

LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy.
Molecular genetics and metabolism reports
Meijer IA and Sasarman F and Maftei C and Rossignol E and Vanasse M and Major P and Mitchell GA and Brunel-Guitton C
DOI: 10.1016/j.ymgmr.2015.10.010
PubMed: 28649549
11/2015

Mitochondrial Diseases and Cardiomyopathies.
The Canadian journal of cardiology
Brunel-Guitton C and Levtova A and Sasarman F
DOI: 10.1016/j.cjca.2015.08.017
PubMed: 26518446
08/2015

An N-terminal formyl methionine on COX 1 is required for the assembly of cytochrome c oxidase.
Human molecular genetics
Hinttala R and Sasarman F and Nishimura T and Antonicka H and Brunel-Guitton C and Schwartzentruber J and Fahiminiya S and Majewski J and Faubert D and Ostergaard E and Shoubridge EA
DOI: 10.1093/hmg/ddv149
PubMed: 25911677
04/2015

Normal Cerebrospinal Fluid Pyridoxal 5'-Phosphate Level in a PNPO-Deficient Patient with Neonatal-Onset Epileptic Encephalopathy.
JIMD reports
Levtova A and Camuzeaux S and Laberge AM and Allard P and Brunel-Guitton C and Diadori P and Rossignol E and Hyland K and Clayton PT and Mills PB and Mitchell GA
DOI: 10.1007/8904_2015_413
PubMed: 25762494
03/2015

The 3' addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1.
Human molecular genetics
Sasarman F and Thiffault I and Weraarpachai W and Salomon S and Maftei C and Gauthier J and Ellazam B and Webb N and Antonicka H and Janer A and Brunel-Guitton C and Elpeleg O and Shoubridge EA
DOI: 10.1093/hmg/ddv044
PubMed: 25652405
02/2015

De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy
Human Mutation
Lee, J.-R. and Srour, M. and Kim, D. and Hamdan, F.F. and Lim, S.-H. and Brunel-Guitton, C. and D{\'e}carie, J.-C. and Rossignol, E. and Mitchell, G.A. and Schreiber, A. and Moran, R. and Van Haren, K. and Richardson, R. and Nicolai, J. and Oberndorff, K.M.E.J. and Wagner, J.D. and Boycott, K.M. and Rahikkala, E. and Junna, N. and Tyynismaa, H. and Cuppen, I. and Verbeek, N.E. and Stumpel, C.T.R.M. and Willemsen, M.A. and de Munnik, S.A. and Rouleau, G.A. and Kim, E. and Kamsteeg, E.-J. and Kleefstra, T. and Michaud, J.L.
DOI: 10.1002/humu.22709
2015

Scoping review of patient- and family-oriented outcomes and measures for chronic pediatric disease
BMC Pediatrics
Khangura, S.D. and Karaceper, M.D. and Trakadis, Y. and Mitchell, J.J. and Chakraborty, P. and Tingley, K. and Coyle, D. and Grosse, S.D. and Kronick, J.B. and Laberge, A.-M. and Little, J. and Prasad, C. and Sikora, L. and Siriwardena, K. and Sparkes, R. and Speechley, K.N. and Stockler, S. and Wilson, B.J. and Wilson, K. and Zayed, R. and Potter, B.K. and Austin, V. and Feigenbaum, A. and Nagy, L. and Brownwell, M. and Brunel, C. and Casey, R. and Chan, A. and Jain, S. and Chapman, M. and Dyack, S. and Gillis, J. and Dodds, L. and Fell, D. and Geraghty, M. and Langley, E. and Giezen, A. and Ueda, K. and Vallance, H. and Greenberg, C. and Guttmann, A. and Hayeems, R. and Miller, F. and Khan, A. and MacKenzie, J. and Maranda, B. and Mhanni, A. and Mitchell, G. and Nakhla, M. and Pender, A. and Potter, M. and Turner, L. and van Karnebeek, C.
DOI: 10.1186/s12887-015-0323-x
2015

Inborn errors of cytoplasmic triglyceride metabolism.
Journal of inherited metabolic disease
Wu JW and Yang H and Wang SP and Soni KG and Brunel-Guitton C and Mitchell GA
DOI: 10.1007/s10545-014-9767-7
PubMed: 25300978
10/2014

Late-onset nonketotic hyperglycinemia caused by a novel homozygous missense mutation in the GLDC gene.
Molecular genetics and metabolism
Brunel-Guitton C and Casey B and Coulter-Mackie M and Vallance H and Hewes D and Stockler-Ipsiroglu S and Mercimek-Mahmutoglu S
DOI: 10.1016/j.ymgme.2011.02.009
PubMed: 21411353
02/2011

Treatment of cobalamin C (cblC) deficiency during pregnancy.
Journal of inherited metabolic disease
Brunel-Guitton C and Costa T and Mitchell GA and Lambert M
DOI: 10.1007/s10545-010-9202-7
PubMed: 20830523
09/2010

LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria.
Molecular biology of the cell
Sasarman F and Brunel-Guitton C and Antonicka H and Wai T and Shoubridge EA and LSFC Consortium
DOI: 10.1091/mbc.E10-01-0047
PubMed: 20200222
03/2010

Enzyme replacement therapy in pediatric patients with Gaucher disease: What should we use as maintenance dosage?
Molecular Genetics and Metabolism
Brunel-Guitton, C. and Rivard, G.-E. and Galipeau, J. and Alos, N. and Miron, M.-C. and Therrien, R. and Mitchell, G. and Lapierre, G. and Lambert, M.
DOI: 10.1016/j.ymgme.2008.11.158
2009

Research

Knocking mouse model and role of CMPK2 in mitochondrial dNTP metabolism
Creation of a knocking mouse model to further characterize the role of CMPK2 in mitochondrial dNTP metabolism and to test the efficacy of a supplemental therapy, CHU Sainte-Justine.

RNA sequencing in undiagnosed myopathies
Collaboration for RNA sequencing in undiagnosed myopathies after normal WES and mitochondrial DNA sequencing, CHU Sainte-Justine, University of Montreal and Collaboration with BC Children's Hospital in process.

Cardiovascular evaluation and exercise intolerance characterization of patients
Collaboration with the department of kinesiology and cardiology to establish a cardiovascular evaluation and exercise intolerance characterization of patients with various type of myopathies, followed by the establishment of exercise programs

Grants

Creation of a knocking mouse model to further characterize the function of CMPK2, a nuclear-encoded gene involved in mitochondrial dNTP metabolism and identified in a patient with a mitochondrial disease ressembling mitochondrial neurogastrointestinal encelphalopathy and to test the efficacy of a supplemental therapy. Funding from Rare Diseases

Models & Mechanisms Network (RDMN) Network

Funding to support the development of the mitonchondrial diseases functional analysis in the biochemical genetics diagnostic laboratory, CHU Sainte-Justine. Funding from Genzyme-Sanofi

Project Go Mimo

Functional analysis of new variants identified in children with mitochondrial diseases

TRNT1, DNLZ, HARS2, NDUFA4, NDUFA8. Funding from Fondation Pierre-Lavoie

Honours & Awards

2010 Nomination InCytes for article of the year, co-first author

LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria

Previously, Canadian National Team Member Rock Climbing, CEC Climbing Escalade Canada