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.

____________________________________________________________________________________




When Nolin was just three years old he became the first person in the world to be diagnosed with NANS deficiency, a genetic disorder that causes severe neonatal epilepsy, bone abnormalities, and developmental arrest. The problem lies in the body’s inability to make enough sialic acid, a sugar which provides building blocks for many processes in the body.

The diagnosis, made by the clinician-researchers at TIDE-BC, had a profound effect not only on Nolin’s access to care but also in providing support for his parents, Darlene and Frank.

NANS deficiency is a truly devastating condition. Nolin is missing a critical enzyme that affects the development of many of the body’s tissues and cells. As a result, he cannot hold up his head, sit, stand, eat orally, talk or see very well. He needs 24 hours of care, a feeding tube, is prone to airway infections and blood complications, in short, he is completely dependent on others.


Nolin is described along with 8 other individuals with NANS deficiency, a novel inborn error of metabolism, in a recent Nature Genetics article.



READ MORE...
___________________________________________
Together with the dieticians in BC Children's Hospital, we've created an exciting line-up of diet apps. These apps are designed to support families and children who suffer very rare disorders like: Maple Syrup Urine Disease, Pyridoxine dependent epilepsy, Phenylketonuria and 12 others.You can read more about these apps and try them out via this link:http://www.metabolicdietapp.org
READ MORE...
___________________________________________


Logan is an 18-year old who loves to play hockey, swim with dolphins and take the occasional spin around Orlando Speedway. As part of his recent graduation events he participated in a seven day hiking trip in the Rocky Mountains, in a trail rider with his classmates and father close by. The fact that Logan has neurodegenerative disease which severely restricts his independent mobility does not stop him. As his father, Rick, says, “We just adapt and find a way to make it happen.”

Logan Miller has an ultra-rare disease – the cause of which has, for the past 14 years, remained undiagnosed. Now researchers believe they may be close to a diagnosis. In fact, the decision to enroll Logan into the genomics study has brought the Miller family the closest they’ve been to understanding their son’s disease since it first became apparent he was not developing at the same pace as his peers. He went on to suffer memory loss, muscle weakness and eye movement problems.

“We enrolled him because Logan has always wanted a diagnosis, and we want to know, not least because his illness is progressive,” said Debbie Miller, Logan’s mother. “This study seemed a good fit.”


READ MORE...
___________________________________________
A study is currently underway at TIDE, designed to evaluate the safety and efficacy of a novel treatment for glucose transporter deficiency syndrome (Glut1-DS), a rare genetic epilepsy caused by insufficient transport of sugar into the brain, often resulting in developmental delays. A ketogenic diet is standard treatment but in some cases this does not control the seizures and movement disorder. Triheptanoin/C7 oil could provide an alternative source of fuel for the brain, thereby improving brain function and development. In collaboration with Ultragenyx Inc, the company supplying the investigational drug, the study, designed by the TIDE team, is using innovative trial methodology for rare diseases and has obtained approvals from Health Canada and REB. The first patient was enrolled on April 15th and the next phase protocols for further clinical development of Triheptanoin are currently being planned. If successful, this personalized approach to treating Glut1-DS could serve as a model for eliminating seizures and side effects in other types of hard-to-treat epilepsies.

The study is actively recruiting GLUT1-DS patients across Canada Interested?
Please contact us via email: tide-bc@cw.bc.ca

READ MORE...
___________________________________________
The Lysine –Restricted Diet as Novel Add-On Therapy for Pyridoxine Dependent Epilepsy: PDE Consortium’s Consensus Recommendations

Among the most recent TIDE publications are the consensus recommendations for lysine –restricted diet as new add-on therapy for PDE. This paper is the result of several international PDE Consortium Workshops (2010-2013), a platform uniting expert physicians and scientists in the field of this metabolic epilepsy. Published in JIMD Reports, these Recommendations aim to standardize the implementation and monitoring of patients using the new diet in addition to vitamin B6 treatment, with the goal of improving neurodevelopmental outcomes: about 75% of patients with PDE due to antiquitin (ATQ) deficiency suffer from developmental delay and/or intellectual disability despite receiving treatment for seizures. The 2012, a landmark paper by Dr. Clara van Karnebeek in collaboration with Canadian, German (Dr. Hans Hartmann and colleagues) and USA (Dr. Johan Van Hove and colleagues) centers, showed that adjunctive treatment with a lysine-restricted diet is safe, and prevents brain damage via lowering toxic lysine intermediates in the brain. Potential benefits included seizure control and improved psychomotor development in this patient population.
READ MORE...
___________________________________________
CIMDRN-Eng-Burgundy
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).
READ MORE...
___________________________________________
MajaTarailoGraovac
Who I Am
I am a geneticist who combines knowledge and training in biochemistry, medical genetics, cell biology, bioinformatics, arts and teaching to accelerate discovery of new pathogenic variants of known and unknown genes that lead to disease, using whole exome sequencing (WES) and whole genome sequencing (WGS) methods.

What I do for TIDE
I am leading Wasserman’s group in applied genome analysis efforts to develop efficient methods with which to utilize next generation sequencing (NGS) advances and facilitate their translation into clinical practice. As a member of TIDE’s computational research team, we have successfully established a computational pipeline for high throughput processing of sequencing data, variant calls, variant prioritization and optimal delivery of visual and understandable candidate variant lists for clinicians. Currently, using this pipeline in our trio-based analysis (father-mother-child), we are able to process raw fastq sequencing files and deliver an annotated list of variants to clinicians in 1-2 days (8-16 hours).

Special accomplishments for TIDE
At TIDE, we work as a family to combine our strengths for timely diagnosis of rare genetic diseases. We work around the clock with hopes of discovering new/optimal treatments thereby improving lives of patients and their families at BCCH and beyond.
READ MORE...
___________________________________________
The TIDEX team publishes their new discovery: "Carbonic anhydrase VA deficiency as novel and treatable cause of hyperammonemia in the young child" in the American Journal of Human Genetics, February 2014 (click here for the Epub ahead of print).

newborn
Read more about the research of our UBC team in collaboration with colleagues in the USA, UK, and Australia, via the UBC Faculty of Medicine website ("Genetic discovery helps newborns beat a life-threatening condition").



READ MORE...
___________________________________________
VIEW OLDER POSTS...