Nathan: the story of a family’s journey through the discovery of a treatable intellectual disability

Five-year old Nathan and his family have experienced a life-changing journey during the course of his short life. At the age of three, suffering from seizures but undiagnosed despite having seen 15 specialists, Nathan was diagnosed by the team at TIDE-BC with Creatine Transporter Deficiency, a severe, incurable neurological disease affecting all aspects of life.
As a result of the diagnosis, Nathan was prescribed “causal therapy” consisting of amino acid and creatine supplements. These have resulted in a dramatic improvement in Nathan, as is evident on imaging as well as in his cognitive and behavioural functioning, and equally importantly, peace of mind for his family, as they move forward.
Nathan appeared healthy until roughly eight months, when his parents, Ian and Vanessa, noticed that he wasn’t reaching milestones they had seen in his older sister.

Initially, it appeared that Nathan might have been deaf but his significant behavioural disturbances and cognitive delays were suggestive of something else. Seen by many specialists in Phoenix, AZ, where the family lived at the time, autism seemed a possible diagnosis, but agreement among the care providers, a group that included developmental pediatrics, neurology, psychiatry, and speech pathology, was never achieved.
“Nathan had such low muscle tone, he would fall all the time when he walked. He had so many bruises. I remember the looks we used to get.”
Vanessa
Despite the lack of a diagnosis, the family found a school in which to enroll their son. Comprised of a team of allied health care providers, Nathan was able to grow and develop in that nurturing environment to the best of his ability. However, not long after starting at school the family was transferred to Vancouver for Ian’s work. This proved to be a challenging time for the family, specifically regarding how best to support Nathan.

Receiving a Diagnosis

Upon arrival in Vancouver, Nathan was referred to Sunny Hill Health Centre for Children for evaluation by a developmental pediatrician, and subsequently by specialists in psychology and speech/language pathology, and finally, neurology.

By now, Nathan had been seen by 15 specialists. As was the case in Phoenix, Autism was considered a possible diagnosis, but again, no consensus was reached. However, neurologist Dr. Vann Chau, at BC Women's Hospital & Health Centre, conducted an in-depth work up for Nathan and discovered excessive creatine in the urine.

Creatine, a chemical substance that plays a role in supplying energy to cells, was discovered almost 20 years ago by Dr. Stockler, currently Head of the Biochemical Diseases Division in BC Children’s Hospital, and TIDE-BC. Because the brain is a ‘high energy consumer,’ in cases where creatine is insufficiently transported to the brain developmental and neurological problems can result. The excessive creatine in Nathan’s urine suggested a possible diagnosis of Creatine Transporter Deficiency. Sure enough, an MRI spectroscopy revealed minimal levels of creatine in Nathan’s brain. The imaging results, in conjunction with consultation with Dr. Clara van Karnebeek, a pediatrician who specializes in biochemical diseases affecting the brain, and co-leader of TIDE-BC BCCH, confirmed the diagnosis. Importantly, further testing revealed the presence of a defect in Nathan’s X chromosome that prevents the manufacture of a normally functioning creatine transporter.

Dr. Chau credits the TIDE-BC program with enabling the diagnosis. “Now that we have the TIDE study with a comprehensive testing protocol we are enhancing our ability to diagnose intellectual disabilities which are causally treatable,” he said.
“We are very grateful to Dr. Vann Chau for his meticulous review of Nathan’s results and subsequent follow up to the autism assessment at Sunny Hill. This led to Nathan’s diagnosis by Dr. Clara Van Karnebeek.”
Vanessa
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“Our experience of developmental disability has been that a diagnosis as specific as Nathan’s is rare and we are fortunate that Nathan’s diagnosis is specific. This gives us confidence that all of his team, including us, are working hard on the appropriate solution. We did not always have this certainty and given that research shows important gains are made by early intervention it is stressful not being certain that you are intervening appropriately.”
Ian

Receiving Treatment

While Creatine Transporter Deficiency is not curable, it is treatable, thanks to an innovative therapy initiated by Dr. van Karnebeek for Nathan. That therapy consists of creatine, glycine and arginine supplements administered three times a day to enhance existing brain creatine content. This treatment requires Nathan to drink a lot of water during the day, to protect his kidneys. This proved to be a further hurdle, as Nathan doesn’t like water. However, another plan was devised. With the support of Tree House, a progressive school in West Vancouver that Nathan is currently attending, and with allied health partners, all the children in Nathan’s class give him a pre-determined amount of water each day. Not only is Nathan’s fluid intake monitored, but the children in his class are also helping to support Nathan in his journey.

In addition to the supplements Nathan also receives two to three hours of private behavioural modification therapy every day. While the entire family supports Nathan, as does the Tree House school, Vanessa also dedicates a great deal of her time to helping Nathan one-on-one, and she notes that her background as a preschool teacher has been quite helpful in supporting Nathan’s developmental needs.

Proof that the supplement therapy was working came in May 2012: MRI spectroscopy showed that compared with the previous scan in 2011, Nathan had higher levels of creatine in his brain. Although the levels of creatine are far from normal, the therapy clearly has an effect on the creatine content in Nathan’s brain. Observing Nathan, it is apparent that his cognitive-behavioural functioning has drastically improved. He can communicate, interact and demonstrates empathy. Nathan’s older sister has noticed a difference in her brother and has told her Vanessa ‘mommy Nathan’s going to be better.’
“Nathan used to smash his head against the wall and could not communicate. The other day he stood at the window singing that the sun was shining. He couldn’t talk before. Now he shows empathy to his sister when she is upset, saying lovingly ‘Emma, my sister’. This is amazing to us.”
Vanessa

The Importance of Early Diagnosis

Dr. van Karnebeek, who founded TIDE-BC with Dr. Stockler, emphasizes the importance of early recognition of disorders such as Nathan’s.

‘Early recognition allows for timely treatment, which prevents or minimizes brain damage. There are now more than 81 of such treatable rare conditions causing intellectual disability and related problems such epilepsy and autistic features. TIDE is the first worldwide to systematically implement a protocol prioritizing the identification of these treatable diseases in global delay or intellectual disability, so as to ensure that each affected child can reach its full potential. Each of the 81 genetic conditions is very rare, but as a group these treatable IDs likely account for a few percent of all children with intellectual disability, which is considerable in view of the fact that ID affects 2-3% of all children worldwide. TIDE demonstrates how cutting edge research can be translated from bench to bedside to benefit the patient and society as a whole through improved health outcomes and related cost-savings. I feel honored to work with families such as Nathan’s, and respect their resilience and optimism, learning from them each day.’

The Road Ahead

The family is now moving back to Phoenix. The specialists from BCCH have already spoken with the team in Phoenix to ensure that Nathan’s needs are well understood. The neurologist involved in Nathan’s care before the family moved to Vancouver, Dr. Alarcio, will take over Nathan’s case.. ‘We’re very grateful we know someone there, someone who knows us as a family. We found out that she has a similar case so is familiar with Creatine Transporter Deficiency.

When asked how the family has coped along this journey Vanessa encourages taking each day as it comes and accepting help.
“Take each day as it comes and don’t expect wonders. It’s a slow and emotional journey. As a family it’s hard. If you need help don’t close yourself in. Ask for it. Don’t be shy or feel embarrassed. We wondered how we would ever cope. It takes time. I have learned so much from Nathan about what a person can do. And there’s hope with today’s advancing technology. It’s evolving so fast.”
Vanessa

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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)
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