Overview

The main focus of my work is the investigation of the complex series of events at the cellular and tissue level that are at play in the evolution and of genetic disease. It is hoped that an understanding of disease at this level will result in the development of specific forms of therapy for rare genetic disease. My group has chosen to focus on a series of devastating progressive disorders termed lysosomal storage diseases.

Publications

Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry
Clinical Genetics
Lorne A. Clarke and Roberto Giugliani and Nathalie Guffon and Simon A. Jones and Hillary A. Keenan and Maria V. Munoz-Rojas and Torayuki Okuyama and David Viskochil and Chester B. Whitley and Frits A. Wijburg and Joseph Muenzer
DOI: 10.1111/cge.13583
07/2019

RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit—successes and challenges
European Journal of Pediatrics
DOI: 10.1007/s00431-019-03399-4
06/2019

Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2019.03.010
05/2019

Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management
Journal of Pediatrics
DOI: 10.1016/j.jpeds.2016.11.036
2016

Implementing evidence-driven individualized treatment plans within Morquio A Syndrome
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2015.12.157
2016

Is it Fabry disease?
Genetics in Medicine
DOI: 10.1038/gim.2016.55
2016

12year follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: The important role of early treatment
BMC Medical Genetics
DOI: 10.1186/s12881-016-0284-4
2016

The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders
Best Practice and Research: Clinical Endocrinology and Metabolism
DOI: 10.1016/j.beem.2014.08.010
2015

Characterization of early disease status in treatment-naive male paediatric patients with fabry disease enrolled in a randomized clinical trial
PLoS ONE
DOI: 10.1371/journal.pone.0124987
2015

Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2014.09.012
2015

Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): Under-recognized and challenging to diagnose
Skeletal Radiology
DOI: 10.1007/s00256-013-1797-y
2014

Transgenic mice expressing human glucocerebrosidase variants: Utility for the study of Gaucher disease
Blood Cells, Molecules, and Diseases
DOI: 10.1016/j.bcmd.2013.03.006
2013

Fetal progeria: Prenatal sonographic findings in petty syndrome
Journal of Ultrasound in Medicine
DOI: 10.7863/ultra.32.5.881
2013

Biomarkers
Advances in Gaucher Disease: Basic and Clinical Perspectives
DOI: 10.2217/EBO.12.189
2013

Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure
Orphanet Journal of Rare Diseases
DOI: 10.1186/1750-1172-7-2222524701
2012

The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus
European Journal of Pediatrics
DOI: 10.1007/s00431-011-1606-3
2012

Longitudinal observations of serum heparin cofactor II-thrombin complex in treated Mucopolysaccharidosis i and II patients
Journal of Inherited Metabolic Disease
DOI: 10.1007/s10545-011-9369-6
2012

Biomarkers for the mucopolysaccharidoses: Discovery and clinical utility
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2012.05.003
2012

Production of a-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease
Nature Communications
DOI: 10.1038/ncomms2070
2012

Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants
Glycobiology
DOI: 10.1093/glycob/cwr157
2012

Left ventricular aneurysm in an adult patient with mucopolysaccharidosis type I: Comment on pathogenesis of a novel complication
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2012.06.001
2012

Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure
Orphanet Journal of Rare Diseases
DOI: 10.1186/1750-1172-7-22
2012

Pathogenesis of skeletal and connective tissue involvement in the mucopolysaccharidoses: Glycosaminoglycan storage is merely the instigator
Rheumatology
DOI: 10.1093/rheumatology/ker395
2011

Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms
Circulation Research
DOI: 10.1161/CIRCRESAHA.111.248161
2011

Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2009.08.002
2010

Corrigendum to "Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation" [Mol. Genet. Metab. 99 (2010) 62-71] (DOI:10.1016/j.ymgme.2009.08.002)
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2009.12.013
2010

Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up
Pediatrics
DOI: 10.1542/peds.2009-1728
2010

Imaging of enzyme replacement therapy using PET
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1003247107
2010

Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice
Journal of Clinical Investigation
DOI: 10.1172/JCI31474
2010

Mucopolysaccharidosis I: Management and treatment guidelines
Pediatrics
DOI: 10.1542/peds.2008-0416
2009

Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I
Pediatrics
DOI: 10.1542/peds.2007-3847
2009

The mucopolysaccharidoses: A success of molecular medicine (Expert Reviews in Molecular Medicine (2008) 10, (e1) DOI: 10.1017/S1462399408000550)
Expert Reviews in Molecular Medicine
DOI: 10.1017/S1462399409001185
2009

Production and characterization of soluble human lysosomal enzyme a-iduronidase with high activity from culture media of transgenic tobacco BY-2 cells
Plant Science
DOI: 10.1016/j.plantsci.2009.08.016
2009

Intracranial calcification after cord blood neonatal transplantation for Krabbe disease
Neuropediatrics
DOI: 10.1055/s-0029-1243189
2009

Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities
American Journal of Pathology
DOI: 10.2353/ajpath.2009.090211
2009

Pharmacokinetics of sapropterin in patients with phenylketonuria
Clinical Pharmacokinetics
DOI: 10.2165/0003088-200847120-00006
2008

Characterization of Fabry Disease in 352 Pediatric Patients in the Fabry Registry
Pediatric Research
DOI: 10.1203/PDR.0b013e318183f132
2008

Heparin cofactor II-thrombin complex: A biomarker of MPS disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2008.05.001
2008

The mucopolysaccharidoses: A success of molecular medicine
Expert Reviews in Molecular Medicine
DOI: 10.1017/S1462399408000550
2008

Idursulfase for the treatment of mucopolvsaccharidosis II
Expert Opinion on Pharmacotherapy
DOI: 10.1517/14656566.9.2.311
2008

Generation of a conditional knockout of murine glucocerebrosidase: Utility for the study of Gaucher disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2006.09.008
2007

A Phase III Extension Study of Aldurazyme®(Laronidase) in Mucopolysaccharidosis I
Clinical Therapeutics
DOI: 10.1016/S0149-2918(07)80472-3
2007

Mucopolysaccharidosis II
Lysosomal Storage Disorders
DOI: 10.1007/978-0-387-70909-3_25
2007

Mucopolysaccharidosis I
Lysosomal Storage Disorders
DOI: 10.1007/978-0-387-70909-3_24
2007

Synthesis of enzymatically active human a-L-iduronidase in Arabidopsis cgl (complex glycan-deficient) seeds
Plant Biotechnology Journal
DOI: 10.1111/j.1467-7652.2005.00166.x
2006

A hemizygous SCO2 mutation in an early onset rapidly progressive, fatal cardiomyopathy
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2006.04.016
2006

Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: Implications for assessment of therapeutic interventions in Hurler syndrome
Pediatric Research
DOI: 10.1203/01.pdr.0000190579.24054.39
2006

Heparin cofactor II-thrombin complex in MPS I: A biomarker of MPS disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2006.01.005
2006

Submicroscopic deletions and duplications in individuals with intellectual disability detected by Array-CGH
American Journal of Medical Genetics
DOI: 10.1002/ajmg.a.31015
2005

A homology model for human a-L-iduronidase: Insights into human disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2004.12.006
2005

Long-Term Follow-Up of Three Individuals with Kabuki Syndrome
American Journal of Medical Genetics
2004

Spasms in children with definite and probable mitochondrial disease
European Journal of Neurology
DOI: 10.1046/j.1351-5101.2003.00724.x
2004

Pseudo-lysosomal storage disease caused by EMLA cream
Journal of Inherited Metabolic Disease
DOI: 10.1023/B:BOLI.0000037352.98317.5a
2004

Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human a-L-iduronidase (laronidase)
Journal of Pediatrics
DOI: 10.1016/j.jpeds.2004.01.046
2004

Sequence analysis of the mitochondrial genomes from Dutch pedigrees with leber hereditary optic neuropathy
American Journal of Human Genetics
DOI: 10.1086/375537
2003

Family 39 a-L-iduronidases and ß-D-xylosidases react through similar glycosyl-enzyme intermediates: Identification of the human iduronidase nucleophile
Biochemistry
DOI: 10.1021/bi034293v
2003

Mucopolysaccharidosis type VII (Sly syndrome) presenting as neonatal cholestasis with hepatosplenomegaly
Journal of Pediatric Gastroenterology and Nutrition
DOI: 10.1097/00005176-200108000-00025
2001

Recombinant proteins for genetic disease
Clinical Genetics
DOI: 10.1034/j.1399-0004.1999.550601.x
1999

Murine MPS I: Insights into the pathogenesis of Hurler syndrome
Clinical Genetics
1998

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome
American Journal of Human Genetics
1997

Murine mucopolysaccharidosis type I: Targeted disruption of the murine a-L-iduronidase gene
Human Molecular Genetics
DOI: 10.1093/hmg/6.4.503
1997

Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes
Nature Genetics
DOI: 10.1038/ng1096-174
1996

Isolated mitochondria from frozen muscle have limited value in diagnostics
European Journal of Pediatrics
DOI: 10.1007/BF01972981
1995

Molecular genetics of muccpolysaccharidosis type I: Diagnostic, clinical, and biological implications
Human Mutation
DOI: 10.1002/humu.1380060403
1995

Erratum: Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm (Nature Genetics (1994) 6 (409-413))
Nature Genetics
1994

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm
Nature Genetics
DOI: 10.1038/ng0494-409
1994

Stability of frozen muscle used for mitochondrial enzyme assays
European Journal of Pediatrics
DOI: 10.1007/BF01959232
1994

Tetrasomy 12p (Pallister-Killian syndrome): Ultrasound indicators and confirmation by interphase fish
Prenatal Diagnosis
DOI: 10.1002/pd.1970140904
1994

Murine a-l-Iduronidase: cDNA Isolation and Expression
Genomics
DOI: 10.1006/geno.1994.1621
1994

Reports: Linkage of pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity
Human Molecular Genetics
DOI: 10.1093/hmg/3.12.2153
1994

Mutation analysis of 19 North American mucopolysaccharidosis type I patients: Identification of two additional frequent mutations
Human Mutation
DOI: 10.1002/humu.1380030316
1994

Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia
Arteriosclerosis, Thrombosis, and Vascular Biology
1994

Erratum: A transcription map of the region containing the Huntington disease gene (Human molecular genetics (1993) 2 (901-907))
Human Molecular Genetics
1993

Two novel mutations causing mucopolysaccharidosis type i detected by single strand conformational analysis of the a-L-iduronidase gene
Human Molecular Genetics
DOI: 10.1093/hmg/2.8.1311
1993

A PCR method for accurate assessment of trinucleotide repeat expansion in huntington disease
Human Molecular Genetics
DOI: 10.1093/hmg/2.6.635
1993

A transcription map of the region containing the huntington disease gene
Human Molecular Genetics
DOI: 10.1093/hmg/2.7.901
1993

Long term survival of an infant with sirenomelia
American Journal of Medical Genetics
DOI: 10.1002/ajmg.1320450303
1993

Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease
Nature
1993

Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy
American Journal of Human Genetics
1992

Cloning and mapping of the a-adducin gene close to D4S95 and assessment of its relationship to huntington disease
Human Molecular Genetics
DOI: 10.1093/hmg/1.9.669
1992

Mitochondrial disorders in pediatrics: Clinical, biochemical, and genetic implications
Pediatric Clinics of North America
1992

A mutation in the human lipoprotein lipase gene as the most common cause of familial chylomicronemia in French Canadians
New England Journal of Medicine
1991

Sudden, unexpected, natural death in childhood
Fetal and Pediatric Pathology
DOI: 10.3109/15513819009064711
1990

Crystal diaper syndrome.
CMAJ : Canadian Medical Association journal = journal de l"Association medicale canadienne
1989

Research

Clinical trial of BH4 for the treatment of classical PKU
It has now been suggested that small molecules can act as chemical chaperones for misfolded proteins that are caused by point mutations of genes. PKU is an inborn error of metabolism that is currently treated by very restrictive diet. In vitro studies have shown that BH4 can stabilize mutant PAH enzyme and lead to greater tolerance of PHE in the diet.

Proteomic approach to the identification of biomarkers of MPS disease
This project involves the identification, through serum proteomic studies, markers of disease severity and responsiveness. Markers will initially be identified in a murine model and subsequently validated in human samples.

Clinical trial of recombinant iduronidase in the treatment of MPSI
Clinical trial of recombinant iduronidase in the treatment of MPSI. This is a complex multicenter multinational clinical trial of the use of iduronidase for the treatment of the genetic disease MPS I.

Honours & Awards

Canadian Glyconomics network Award- 2017

Canadian Organization for Rare Disorders (CORD) Rarity Award for Scientific Excellence - 2013.

Research Group Members

Anita Thomas, Research Assistant / Research Technician