A heartbroken mum whose young son has a rare, incurable and deadly disease is urging parents to get their children examined further if medics fail to find a diagnosis.
Amy Sheridan-Hill, aged 43, said medics initially diagnosed her seven-year-old son Frankie with cerebral palsy because he couldn’t walk and his mobility, including sitting up and crawling, was delayed.
But months later, to her horror, Amy and husband Greg, from Ware in Hertfordshire, discovered he suffered from a far more dangerous condition than she could have possibly imagined.
“At first, there was nothing to cause alarm,” she said. “It wasn’t until he was two and still not walking that we knew something was wrong. He was sitting up and crawling, but his motor skills were developing much slower than other children.
“We saw a neurologist when he was four, who diagnosed Frankie with cerebral palsy. He was very confident in the diagnosis. We thought we could deal with that.”
Tragically, it was only after Frankie had an MRI scan and his genome sequenced that he was finally diagnosed with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) – a severe form of a life-threatening disease known as TUBB4a leukodystrophy.
“We were absolutely devastated when we found out,” Amy, who co-founded the H-ABC Foundation charity to raise money for research into the disease, said. “We were advised not to Google it because it might upset us.
“When we looked into leukodystrophy online, the first thing that came up said a child usually dies within two years of diagnosis. I just thought ‘how could this happen to our baby boy?’
“We were shocked with what we found.”
First discovered in 2014, the debilitating and life-threatening condition, which affects the central nervous system, is caused by a mutation in the TUBB4a gene. It disrupts the signals between nerve cells and the brain.
Patients can also develop seizures, muscle contractions, hearing and speech difficulties, and uncontrollable limb movements, while others who have developed motor skills in early childhood can regress.
Babies and children who develop the disease often die by their late teens.
It was initially thought to only affect 200 people worldwide.
However, the latest research suggests the figure could be far higher than first thought.
According to the University of Utah in the US, leukodystrophies affect 1 in 7,663 births. With about 140 million children born globally in 2021, that would mean more than 18,000 could have leukodystrophy – and almost 1,650 with TUBB4a – last year alone.
In fact, researchers fear the number of cases could be higher still because many patients are thought to have been misdiagnosed with other conditions, such as cerebral palsy.
A varied combination of symptoms, some of which are technically separate conditions, makes it incredibly difficult to spot. The only way to confirm the disease is by genome sequencing and an MRI scan.
But there is hope on the horizon.
Oxford-based biotech firm SynaptixBio was launched last year in a bid to develop the world’s first treatment.
The company recently signed a global licencing deal with the Children's Hospital of Philadelphia (CHOP) - the world’s leading TUBB4a leukodystrophy centre - in the US to pursue cutting-edge research into the disease.
SynaptixBio aims to launch clinical trials in 2024.
“This project has the potential to change people’s lives,” Dr Dan Williams, SynaptixBio CEO and co-founder, said. “The research and development of a clinically-proven treatment for TUBB4a would be a real game-changer for patients and their families.”
CHOP has identified Antisense Oligonucleotides (ASOs) as a potential treatment for the disease.
It is hoped ASOs, which have previously been used to treat conditions such as Duchenne muscular dystrophy and spinal muscular atrophy, will dramatically improve the quality of, and extend, the lives of leukodystrophy patients.
“ASOs provide the potential to stabilise, improve quality of life, and extend life expectancy of children suffering from the condition,” Dr Vanderver said. “Successful prevention of leukodystrophy progression would be revolutionary, life-saving, and life-enriching.”
Dr Williams added that the deal was a “huge step forward” in the fight to tackle the condition.
“This landmark agreement will enable SynaptixBio to develop and commercialise CHOP’s patents and research related to the treatment of TUBB4A leukodystrophy.
“We are naturally delighted to be working with CHOP on this extremely important project, which aims to accelerate the research and development of the world’s first treatment for the disease.”
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