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.


An international consortium established by Tide-BC members met early in September 2012 to reach consensus on protocols for implementing and studying dietary lysine restriction as novel treatment for Pyridxone Dependent Epilepsy.
BC Children’s Hospital researchers lead the collaboration of clinicians and researchers across Canada, Europe and the USA, and are publishing exciting first results of an intervention which can dramatically improve outcomes of affected affected patients.

Lysine Restricted Diet for Pyridoxine-Dependent Epilepsy: First Evidence & Future Trials (Article in press: Molecular Genetics and Metabolism)
Clara D.M. van Karnebeek; Hans Hartmann; Sravan Jaggumantri; Levinus Bok; Barb Cheng; Mary Connolly; Curtis R. Coughlin., Anibh M. Das; Sidney M. Gospe; Cornelis Jakobs; Johanneke van der Lee; Saadet Mercimek-Mahmutoglu; Uta Meyer; Eduard Struys; Graham Sinclair, PhD; Johann Van Hove, MD; Jean Paul Collet, MD PhD; Barbara R. Plecko, MD; Sylvia Stockler, MD PhD

See poster presentation for more details.

To evaluate the efficacy and safety of dietary lysine restriction as an adjunct to pyridoxine therapy on biochemical parameters, seizure control, and developmental/cognitive outcomes in children with pyridoxine-dependent epilepsy (PDE) caused by antiquitin (ATQ) deficiency.

Methods: In this observational study, seven children with confirmed ATQ deficiency were started on dietary lysine restriction with regular nutritional monitoring. Biochemical outcomes were evaluated using pipecolic acid and α-aminoadipic semialdehyde (AASA) levels in body fluids; developmental/cognitive outcomes were evaluated using age-appropriate tests and parental observations.

Results: Lysine restriction was well tolerated with good compliance; no adverse events were reported. Reduction in biomarker levels (as measured by the last value before and first value after initiation of dietary lysine restriction) ranged from 20 to 67% for plasma pipecolic acid, 13 to 72% for urinary AASA, 42% for plasma AASA. For the 1 patient in whom data was available, cerebrospinal fluid levels decreased by 87.2% for pipecolic acid and 81.7% for AASA. Improvement in age-appropriate skills and seizure control were observed in all children.

Conclusions: This observational study provides Level IV evidence that lysine restriction is well tolerated with significant decrease of potentially neurotoxic biomarkers in different body compartments, with the potential to improve seizure control and/or developmental outcomes in children with PDE caused by ATQ deficiency. To generate a strong level of evidence before this potentially burdensome dietary therapy becomes the mainstay treatment, we have established: an international PDE consortium to conduct future studies with an all-inclusive integrated study design; a website containing up-to-date information on PDE; a methodological toolbox; and an online registry to facilitate the participation of interested physicians, scientists, and families in PDE research.