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About Sickkids
About SickKids

Andreas Schulze, MD, PhD, FRCPC

The Hospital for Sick Children
Section Head, Metabolic Genetics
Clinical and Metabolic Genetics

Medical Director, Newborn Screening Program
Department of Paediatrics

Research Institute
Senior Associate Scientist
Genetics & Genome Biology

University of Toronto
Department of Paediatrics

Department of Biochemistry

Phone: 416-813-7654 EXT. 301480
Fax: 416-813-4940
Email: andreas.schulze@sickkids.ca

Research Interests

Dr. Schulze is a Clinician Scientist who has spent the past 20+ years conducting medical research at the forefront of Inborn Errors of Metabolism. He, applied new diagnostic techniques like stable isotope tracer metabolic flux studies, LC-MSMS for Expanded Newborn Screening, HPLC guanidino compound analysis, and in vivo MR spectroscopy.

He was the first to report and describe the full biochemical spectrum in GAMT-D and has been a leader in the field of innovative therapies since.

Studying mouse models of AGAT-D and GAMT-D to inform endpoints for small molecule therapies and to delineate the pathophysiology of disease, his research group has established a breadth of biological methods for mouse phenotyping that includes micro-quantification of creatine metabolites and guanidino compounds, in vivo mouse brain [1H] - and [31P] MR spectroscopy, mouse electrocorticography, and quantitative high-resolution mouse brain imaging in close collaboration with other researchers. For two conditions, GAMT-D and Sanfilippo disease, Schulze’s group has identified druggable treatment targets and set up a complete suite of tests for drug discovery, validation and confirmation.

Laboratory Research – Schulze Lab:

“Models, Mechanism, and Management of Inborn Errors of Metabolism”

Schulze’s research group focuses on the following research areas:

  • Creatine Deficiency Syndromes
  • Regulation of Creatine Synthesis
  • Pathophysiology of Guanidino Compounds
  • Small Molecule Treatments

Clinical Research:

  • Quantitative In Vivo Brain Magnetic Resonance Spectroscopy
  • Urea Cycle Defects, especially Arginase Deficiency
  • Gyrate Atrophy (Hyperornithinemia)
  • Glycogen Storage Disorders
  • Galactosemia
  • Defects of Remethylation and Transsulfuration

External Funding

New Therapy for Six Mucopolysaccharidoses. Sanfilippo Children's Foundation, Australia and Cure Sanfilippo, US. Principal Investigator.

Molecular-Functional Imaging of Hypoxia in Childhood Sarcomas: Feasibility Steps towards Personalized Medicine. Society of Pediatric Radiology. Principal Investigator: Doria A. Co-Investigator.

Diagnostic Uncertainty Generated by Newborn Screening for Inborn Errors of Metabolism: Parent, provider, and programmatic perspectives. Center for Genetic Medicine Catalyst Grant. Co-Principal Investigator.

Pre-clinical gene editing for Arginase-1 deficiency.  2015-2016 Urea Cycle Disorders Consortium Research Fellowship in Urea Cycle Disorders. Urea Cycle Disorder Consortium. Co-Principal Investigator.

Rare Diseases Clinical Research Consortia (RDCRC) for the RDCR Network - Urea Cycle Disorder Consortium. National Institute of Child Health and Human Development and National Centre for Advancing Translational Sciences. Site-Principal Investigator.

Longitudinal Study of Urea Cycle Disorders. Children's Research Institute. Site-Principal Investigator.

HPN-009. An Open Label Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate (GPG; RAVICTI) in Pediatric Subjects under Two Years of Age with Urea Cycle Disorders (USCDs).  Hyperion Therapeutics. Site-Principal Investigator.


Click here to view Andreas Schulze's current publications. 

  1. Ÿ Schulze A, Bauman M, Tsai AC, et al.: Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism. Pediatrics 2016: 137(1):1-9;  and
    Ÿ Cameron JM, Levandovskiy V, Roberts W, Anagnostou E, Scherer S, Loh A, Schulze A: Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder. Int J Mol Sci 2017: 18.

Largest and first prospective study to inform the role of impaired creatine metabolism on the neurobiology of autism – Study of 450 children with autism spectrum disorder from three North American autism treatment centers revealed very low prevalence of creatine deficiency syndromes in children with nonsyndromic autism and no genetic association between creatine metabolism and autism.

  1. Tkachyova I, Fan X, LamHonWah AM, Fedyshyn D, Tein I, Mahuran DJ, Schulze A: NDST1 preferred promoter confirmation and identification of corresponding transcriptional inhibitors as substrate reduction agents for multiple mucopolysaccharidosis disorders. PLoS One 2016:11: e0162145.

Proof of principle for substrate reduction therapy (SRT) using small molecule treatments. Data confirm targeting of NDST1 expression has a strong potential to provide a basis of SRT in patients with six different mucopolysaccharidoses. Small molecule therapy has the likely ability to pass through the blood-brain barrier and thus treating the disease in the brain. Our work can serve a strong basis for future research on treatments in other inherited metabolic disorders.

  1. Miscevic F, Foong J, Schmitt B, Blaser S, Brudno M, Schulze A: An MRSpec database query and visualization engine with applications as a clinical diagnostic and research tool. Mol Genet Metab 2016:119:300-306.

Since 2008, we have systematically ascertained quantitative MRS data from more than 4,000 pediatric patients that underwent brain MR spectroscopy at the Hospital for Sick Children. The data were complemented with clinical information. In this manuscript, we report on the development and application of a robust and flexible computational tool for facilitating the exploration of vast metabolite datasets. Open access to our tool and the underlying data base, the largest of its kind in the world, will lead to its widespread use, improving the diagnostic yield and contributing to better understanding of metabolic processes and conditions in the brain.

  1. Schulze A, Tran C, Levandovskiy V, Patel V, Cortez MA: Systemic availability of guanidinoacetate affects GABA(A) receptor function and seizure threshold in GAMT deficient mice. Amino Acids 2016:48:2041-2047.

First demonstration in a preclinical model of guanidinoacetate methyltransferase deficiency (GAMT-D), that (i) mice exhibit electric seizure activity, (ii) seizure activity is GABA(A) receptor mediated, (iii) seizure activity is related to the neurotoxic intermediate guanidinoacetate, and (iv) ornithine has biochemical and electrophysiological efficacy.

  1. Tran C, Yazdanpanah M, Kyriakopoulou L, Levandovskiy V, Zahid H, Naufer A, Isbrandt D, Schulze A: Stable isotope dilution microquantification of creatine metabolites in plasma, whole blood and dried blood spots for pharmacological studies in mouse models of creatine deficiency. Clin Chim Acta 2014: 436C: 160-168.

We developed and validated a new accurate LC-MSMS micro assay for quantification of creatine metabolites in very small blood sample volumes (i.e. 10 µL) that allows to study creatine metabolism and pharmacokinetics in mouse models of creatine deficiency. Validation of the assay in mice revealed plasma creatine metabolites in good accordance with those in patients.

  1. Schulze A, Hoffmann GF, Bachert P, Kirsch S, Salomons GS, Verhoeven NM, Mayatepek E: Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology 2006: 67: 719-721.

The prospective observation in a neonate with GAMT-D, a severe neuro-metabolic disorder, reveals that the biochemical marker guanidinoacetate is already increased at birth. Furthermore, timely start of treatment with creatine, high-dose ornithine, benzoate, and arginine restricted diet leads to normal development in the patient at age 14 month. There were no prior observations (i) that the disease can be diagnosed at birth and by a technology used in newborn screening and (ii) that timely treatment can prevent patients from developing symptoms of the disease. Both the development of the detection method and the new treatment approach has been pioneered by the writer.

  1. Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF: Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics 2003: 111: 1399-1406.

First report on the implementation and the outcome of the expanded newborn screening applying tandem mass spectrometry in a population based approach. The detailed description and the assessment of the first expanded newborn screening program in Europe has helped to implement tandem MS based expanded screening in many newborn screening programs around the globe.

  1. Schulze A, Bachert P, Schlemmer H, et al.: Lack of creatine in muscle and brain in an adult with GAMT deficiency. Ann Neurol 2003: 53: 248-251.

First description of 26 year old GAMT-D patient diagnosed as an adult  - Investigations revealed (i) the disease is severe but not progressive, (ii) the brain can be structural normal, (iii) there is no retinal involvement, (iv) initiation of treatment with creatine, and high-dose ornithine, even if started late, causes significant improvement in cognitive functioning and seizure control. Further, for the first time in men, we could demonstrate the presence of guanidinoacetophosphate in muscle and brain, a compound capable to compensate the deficiency of phosphocreatine.

  1. Schulze A, Ebinger F, Rating D, Mayatepek E: Improving treatment of guanidinoacetate methyl-transferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. Mol Genet Metab 2001: 74: 413-419.

We pioneered a novel treatment in GAMT-D, consisting of Arginine-restricted diet plus low dose Ornithine, that resulted in reduction of guanidinoacetate and cessation of seizures, thus providing proof of principle that (i) guanidinoacetate is neurotoxic and responsible for the drug-resistant epileptic seizures, and that (ii) dietary guanidinoacetate reduction therapy works in patients with GAMT-D.

  1. Schulze A, Hess T, Wevers R, et al.:Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism. J Pediatr 1997: 131: 626-631.

First description of the full biochemical spectrum in GAMT-D in one of the two first patients diagnosed with this disease – GAMT-D represents the first inherited defect of the creatine metabolism in men. The detailed description of GAMT-D resulted in the uncovering of two other inherited diseases of creatine synthesis and –transport, Arginine:Glycine Amidinotransferase deficiency (AGAT-D) and Creatine Transporter defect (CrT-D). GAMT-D, AGAT-D, and CrT-D together comprise Creatine Deficiency Syndromes, a new group of disorders representing a significant though treatable cause of intellectual disability.