Genome test may be key in diagnosing mysterious rare disorders in children

Zahra was four years old when her parents noticed something was wrong.

“Just standing by herself all of a sudden she would just fall down … without any reason,” her father Syed Haider told Global News.

Zahra was struggling with walking, talking and her overall development. Her parents started searching for answers. Despite multiple doctor visits and tests – including genetic testing — two years later they still didn’t know what was wrong with Zahra.

“I used to spend hours and hours in libraries and on the web trying to figure out where is it I should go for answers,” her father said. “There was no clue as to where doctors should be looking.”

It is a story many families whose children suffer from rare disorders can identify with.

“When you have these kids that go through these diagnostic odysseys, it’s really a difficult thing on the families, because they don’t know what’s wrong and you don’t know what the trajectory is,” Dr. Christian Marshall, principal investigator of the study and associate director in the Department of Paediatric Laboratory Medicine at the Hospital for Sick Children (SickKids) told Global News.

READ MORE:  Canadian doctors launch rare disease database

Then Zahra’s family heard of a new study at the Hospital for Sick Children. It was using whole genome sequencing to test for rare genetic disorders and birth defects, instead of using standard genetic testing.

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Whole genome sequencing has been used in research labs but using it for patient diagnosis is a new area. Whole genome sequencing looks at a person’s entire DNA sequence at one time, instead of just one part.

It worked for Zahra: simple blood tests and whole genome sequencing led to an answer. Doctors were able to determine that Zahra suffers from a rare genetic disorder – a one-in-a-million disease.

Sick Kids researchers at the Centre for Genetic Medicine discovered in the 100 babies, children and teens they tested, whole genome sequencing was more accurate than standard genetic testing – a fourfold increase in “diagnostic yield.”

“In order to provide the best possible care, clinicians need to determine the underlying genetic cause. In one test, whole genome sequencing can achieve this. This will help doctors determine prognosis, guide treatment or begin appropriate surveillance and prevention programs if needed,” said Marshall.

Researchers used the whole genome sequencing test for those children and teens with “mystery” difficult-to-diagnose disorders, and discovered it is beneficial for diagnosing the thousands of kids with unexplained developmental delay and or congenital abnormalities, who in many cases are undiagnosed, according to researchers.

Researchers also believe testing using whole genome sequencing would be more cost-effective than standard genetic testing, but add a full economic evaluation is needed. The study was published in the Nature Partner Journals (NPJ) Genomic Medicine.

Zahra has an extremely rare disorder called PKAN, Pantothenate kinase-associated neurodegeneration. PKAN is a progressive neurodegenerative condition with no known cure. For her parents having a diagnosis is a relief.

“Highly doubt (we) would had a diagnosis without the whole genome sequence,” Syed told Global News.

Now he is focussed on caring for his daughter and raising awareness about PKAN.

“It helped my wife and I understand why our daughter is different, and gave us the opportunity to do the best we can for her and find therapies that will improve her quality of life now and as she gets older,” said Haider.

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