Exome sequencing and the management of neurometabolic disorders” , download article here

The metabolic evaluation of the child with an intellectual developmental disorder: Diagnostic algorithm for identification of treatable causes and new digital resource, download article here.


From the 3rd through 5th of April a group of investigators from the University of Ottawa (Dr. Beth Potter, PI, Sara Khangura, manager, the Canadian Inherited Metabolic Diseases Research Network (CIMDRN), Monica Hernandez, REDCap manager and Kylie Tingley, PhD student), representing CIMDRN, visited the Biochemical Diseases team at BC Children’s Hospital, with the objective of discussing a research initiative on PKU to TIDE researchers Drs, Sylvia Stockler, Clara van Karnebeek and Hilary Vallance, who are Vancouver-based co-PIs in CIMDRN. BCCH is among the first Canadian sites to have received ethics review board approval for enrolment of patients in an observational database designed to capture long term outcomes of patients with rare inborn errors of metabolism (IEM). During CIMDRN’s visit, Dr. Potter presented the Network objectives and goals to patients and their families at the BC CanPKU Day (a yearly event for PKU families) together with Dr. Sylvia Stockler, who presented an overview of ongoing clinical studies conducted at the Vancouver campus for and with patients with PKU. The Vancouver team has enrolled the first patients in the PKU database. Dr. Nataliya Yuskiv is coordinating patient enrollment.

PKU, as one of the most frequent, treatable intellectual disabilities, is a CIMDRN priority disease. In BC alone there are approximately 300 individuals, ranging in age from 0-50 years, diagnosed with PKU and every year approximately 4 children are born with this condition province-wide.

Other CIMDRN Initiatives
CIMDRN also includes databases for ultra-rare conditions. Guanidinoacetate methyltransferase deficiency (GAMT) is a treatable intellectual disability with only 80 patients known worldwide. Canada has 8 patients whose longitudinal outcomes will be captured by a CIMDRN database. The database is spearheaded by Dr. Sylvia Stockler who first described this disease in 1996 and recently conducted an international survey on treatments and long term outcomes including 48 patients with this disease (see report last tide newsletter).

Pyridoxine dependent epilepsy (PDE) is another rare condition, and data on a new metabolic treatment (lysine restricted diet) was recently published by the TIDE group showing positive effects (ie, a decrease in toxic biomarkers and improvement neurodevelopment and seizure control). Consequently, Dr. van Karnebeek, together with an international PDE consortium, has published guidelines for this new treatment. She spearheads the CIMDRN PDE registry, the aim of which is to capture Canadian patients with this condition and to assess their long term outcomes; this data will be merged with data from patients around the world.

CIMDRN will also collect data from numerous treatable IEM identified via universal newborn screening. Dr. Hilary Vallance, the director of the BC Neonatal Screening Program, plays an important role in CIMDRN data collections for long term follow-up of patients identified by Canadian newborn screening programs. Approximately 15 children are born a year in BC with conditions investigated by CIMDRN.

Funded by the Canadian Institutes for Health Research (CIHR), CIMDRN integrates nearly all biochemical genetics centers in Canada, and includes investigators with expertise in clinical care of patients with IEMs, as well as epidemiology, health services and policy and health economics.

Overall, the partnership between TIDE and centers within the CIMDRN framework will enable data gathering on treatments and health outcomes for a large group of highly specialized patients and provide the necessary evidence to improve outcomes and health care services for children with IEM and their families, thereby enabling a personalized approach in the care of rare diseases.