Nolin: NANS deficiency, a rare disease diagnosis as a stepping stone towards better care

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 the Treatable Intellectual Disability Endeavour in British Columbia (TIDE-BC), a 5-year program at CFRI and BC Children’s Hospital, 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.
“We went to TIDE just before Nolin turned two. At the time he was having close to 100 seizures a day, and difficulty breathing.”
Darlene
The stress for Nolin’s parents, in caring for their son without knowing the underlying problem, was enormous. “We went to TIDE just before Nolin turned two,” Darlene said. “At the time he was having close to 100 seizures a day, and difficulty breathing.” On one occasion, Nolin stopped breathing on the way to the hospital and his parents had to perform CPR on him, something they’ve had to do several times.

Compounding difficulties was the fact that Nolin’s illness was difficult for the doctors to address because there were so many things going on, Darlene said. But all that changed when he was diagnosed with NANS deficiency. Even though not a great deal is known about his illness, the diagnosis provides background, focus and direction for everyone involved in his care. For example, the diagnosis helped with accessing supportive care. “It was very helpful with eligibility for Make a Wish Foundation, and Canuck place– which was huge,” Frank said. He notes that the diagnosis also helps in accessing much needed funding for care.
Nolin’s diagnosis has also provided the opportunity for Frank and Darlene to connect with other families who have children that are seen by the TIDE Complex Diagnostic Clinic.

Organized by Dr. Clara van Karnebeek, a certified Paediatrician and Biochemical Geneticist, an investigator at CFRI and the Centre for Molecular Medicine and Therapeutics, and an Assistant Professor in the Department of Pediatrics at the University of British Colombia, the clinic brings together specialists from pediatric neurology, biochemical diseases, medical genetics, developmental pediatrics, child and adolescent psychiatry ethics, and any other relevant specialties (orthopedics, gastro-enterology, hematology, rheumatology etc., upon invitation).
It played a huge role in solving the medical mystery of Nolin’s illness. “It ended the diagnostic odyssey,” Darlene said. “Being referred to the clinic and the TIDEX research program (lead bio-informaticians Dr W Wasserman and Dr M Tarailo-Graovac) was one of the greatest things that happened to us. We feel really lucky to have found Dr. van Karnebeek and the TIDE team.”
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“It was frustrating to have to retell your story to many different doctors and never have it really come to anything,” he said. “You never had a sense that people knew about Nolin’s condition. Once we had the diagnosis – everyone was focused in one direction.”
Frank
The clinic continues to coordinate Nolin’s care and so continues to play a huge role in his life, as does BC Children’s Hospital. “The BCCH staff have been amazing – especially the complex care unit – to advocate for us,” Frank said.
Being referred to the TIDE Diagnostic Clinic by Dr T Dewan and Ms A Colllingridge at BC Children's Hospital addressed what Frank sees as the biggest hurdle in getting a diagnosis, which is being seen by one specialist at a time.
“It was frustrating to have to retell your story to many different doctors and never have it really come to anything,” he said. “You never had a sense that people knew about Nolin’s condition. Once we had the diagnosis – everyone was focused in one direction.”
Frank points out that it would be very helpful if more healthcare professionals in the community were aware of the research being done at TIDE –so they could reach out to people who may be candidates for the program.

Today, Nolin is four and a half years old. He goes for walks in his chair with his parents at their home in the countryside. “He likes to play with the iPad – and he seems to be catching on – he can say “My name is Nolin” by hitting a button,” Darlene said. “We have multiple therapists coming to our home. We do music therapy.” They are hoping to raise awareness for Nolin’s condition through their Facebook Page, and raise funds to build a pool so he can have aqua therapy.

Together with colleagues Dr. Superti-Furga and Dr. Luisa Bonafé at the Centre for Molecular Diseases, Lausanne University Hospital, (CHUV), Switzerland, Dr. Ron Wevers and Dr. Dirk Lefeber, at the Translational Metabolic Laboratory, Radboud University Medical Center in Nijmegen, The Netherlands, and a collaborative team of clinicians and scientists involved in identifying and characterizing the eight others with NANS deficiency. The discovery of this novel inborn error of metabolism has been published in Nature Genetics, May 2016.

Additionally, the identification of Nolin’s condition will be published late May 2016 in an overview article reporting the groundbreaking diagnoses and discoveries in over 40 families with an unexplained neurometabolic phenotypes enrolled in the TIDEX program.
For Nolin and the TIDE Team, the next step is to look for potential treatments for NANS deficiency, to replenish the body’s cells and organs with proper sialic acid. This will be challenging and research is ongoing with model organism studies by Dr. Xiao-Yen Wen at the Zebrafish Centre for Advanced Drug Discovery , St. Michael’s Hospital, Toronto, and others around the world. Dr. van Karnebeek is optimistic that one will be found.
“It ended the diagnostic odyssey. Being referred to the clinic and the TIDE research program was one of the greatest things that happened to us.”
Darlene

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TIDE-BC is the first Collaborative Area of Innovation funded through the BC Children's Hospital Foundation, Vancouver, Canada. To expand the project (inter-)nationally funding application is ongoing.

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Contact Information

TIDE BC / Biochemical Diseases Clinic
BC Children's Hospital
Rm K3-208, ACB
4480 Oak Street
Vancouver, B.C. V6H 3V4

Phone: 604-875-2628 (administrative)
Phone: 604-875-2880 (clinic)
FAX: 604-875-2349