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.


The TIDE team has led a new collaboration of clinicians and scientists from across Canada, the USA and Europe investigating dietary lysine restriction as a novel treatment in addition to standard pyridoxine therapy for Pyridoxine-Dependent Epilepsy (PDE). The problem that the TIDE set out to solve: Pyridoxine controls seizures but the accumulation of potentially neurotoxic metabolites (biomarkers) continues, causing cognitive impairments and developmental delays in 75% or more of patients. A diet low in lysine can prevent buildup of toxic waste products caused by the enzyme deficiency underlying this metabolic epilepsy. Preliminary study results implemented in 7 children have been published (onlink to the whole PDE article in Mol Genet Metab) and are most encouraging. Dietary lysine restriction in addition to pyridoxine resulted in significant reduction of all damaging biomarkers, with good tolerance and compliance. No adverse events were reported and improvements in age-appropriate skills in 4 out of 5 children were noted and seizure control was maintained or improved in 6 out of 7 children.

A larger study is needed in order to generate a stronger level of evidence for the positive effect on neurodevelopmental outcomes and safety of this novel intervention. To this end Sylvia Stockler, Sravan Jaggumantri, JP Collet and Clara van Karnebeek of TIDE have established the international PDE consortium www.pdeonline.org and applied for more research funding. The mission of this group of more than 30 researchers and physicians worldwide is to conduct future studies using novel trial designs for small patient numbers and digital tools such online registries, research databases, diet APPs, website and social media. The goal is a united effort to treat and care for those with rare diseases.