Baby’s ‘nagging cough’ leads to shock diagnosis of rare, incurable and deadly disease

2023-06-14

Christian Leduc suffers from TUBB4A leukodystrophy, which causes disruption to the signals between nerve cells in the brain A devastated mother from Vermont has revealed how a common cough led to her baby being diagnosed with a rare, incurable and deadly disease. Beth Leduc said her family’s world was turned upside down when her then-five-month-old son Christian developed a “nagging cough”. “It lasted for weeks,” the mother-of-two, aged 42, said. “We had to keep taking Christian to see the doctor. It became a weekly visit. “During one of the appointments, his doctor asked whether I always had to support his head. She tried a few tests and each time he was unable to support it. His head kept falling back. “I immediately knew something was seriously wrong.” Having been referred for further tests, a week later Christian was examined by a second doctor, who also expressed concern about his condition. Within days, however, Christian developed a fever and was rushed to hospital, where he was diagnosed with respiratory syncytial virus (RSV) – a common virus similar to the common cold. The youngster was discharged, but was returned to A&E just two days later feeling lethargic and being unable to wake up to feed. “I was terrified,” Beth, said. “We were waiting for hours to be admitted because hospital staff tried to get him fluids intravenously. “Christian was tested for Covid-19 before he was admitted to intensive care while they assessed his results.” While at the hospital, Christian underwent a series of genetic tests, including an MRI scan. “I watched as he slowly fell asleep, and they wheeled him into a room for the procedure,” Beth said. “When it was done, they called me in. He was in a crib with a nurse beside him. She said, ‘If there’s something wrong, they would have been waiting for you to discuss the findings, so things must look OK.’ “I felt so relieved.” Tragically, however, the results revealed a condition far worse than Beth could have possibly imagined. Christian, who is now aged three, was diagnosed with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which is a severe form of TUBB4A leukodystrophy – a rare, debilitating and life-threatening genetic disease, which mainly affects babies and children. “At first, we didn’t realise it was so serious,” she said. “The results found a mutation in the TUBB4A gene and we were told the outcome differs for each child. “But, like any parent, we ended up Googling the disease to find out more. We were devastated at what we read.” First discovered in 2013, TUBB4A leukodystrophy makes up 9% of a group of about 30 rare neurodegenerative disorders known as leukodystrophies. Caused by a mutation in the TUBB4A gene, the disease disrupts myelin surrounding nerves, leading to interruption of the signals between nerve cells in the brain. At its most severe, the condition can lead to significant impairment of motor skills such as walking, sitting up and even swallowing. 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. Currently, there is no cure. “Every aspect of Christian’s life has been affected,” Beth said. “He is not mobile, doesn’t speak and eats via a tube inserted into his stomach. “It has been a complete whirlwind for the family.” According to the University of Utah, leukodystrophies affect 1 in 7,663 births. This means about 20,000 people could develop a leukodystrophy - including more than 2,200 with TUBB4A – each year. However, hope is on the horizon. UK biotech firm SynaptixBio is aiming to develop the world’s first treatment for TUBB4A leukodystrophy, and has recently secured 13.2m ($16.4m) in funding to progress research and hopefully take a treatment into clinical trials next year. The Oxford-based company has teamed up with a world-leading leukodystrophy hospital in the US, the Children’s Hospital of Philadelphia - CHOP, to develop a drug from antisense oligonucleotides (ASOs), which can prevent or alter the production of proteins. 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 TUBB4A patients. The project has also secured two prestigious designations from the Food and Drug Administration (FDA) in the US to develop the treatment. SynaptixBio CEO Dr Dan Williams said the treatment had the potential to “adapt the disease mechanisms, redress motor skills deficiencies and boost survival rates.” “We hope our work will produce a safe and efficacious drug that will have a significant impact on patient lives,” he said. “An effective treatment would transform thousands of people’s lives around the world.” Since Christian’s diagnosis, Beth has teamed up with other patient’s parents in the US and UK to support The H-ABC Foundation, which raises awareness of the disease and funds research. In addition to CHOP, Christian also sees specialists at Massachusetts General and the Boston Children’s Hospital. Beth added, “We want to help future families navigating a rare diagnosis and to spread awareness about leukodystrophy; without awareness, there isn’t knowledge and support for families, and hopefully someday a cure. “I am so excited by the work being done to develop a treatment; for me, right now, supporting Christian is a full-time job that I live day by day.” ENDS