More awareness of Alexander disease, a progressive and disabling brain condition, could stop misdiagnoses and missed treatment opportunities.
Summary
The gene that can cause a terminal brain condition called Alexander disease is almost 200 times more common than previously thought, DNA from UK Biobank participants has revealed. The discovery suggests that not everyone carrying the gene will actually develop the disease – and that doctors need to be more aware of the condition to avoid missing or misdiagnosing it.
The genetic mutation that can cause a rare condition called Alexander disease is almost 200 times more common than previously thought, DNA data from UK Biobank participants have revealed.
Clinicians should be more aware of Alexander disease, seeing that this is not some unbelievably vanishingly rare thing.
Dr David Lynch, University College London, UK
The discovery suggests that not everyone carrying the disease-causing gene will actually develop the disease – and that many people’s symptoms are being misdiagnosed. “Clinicians should be more aware of Alexander disease, seeing that this is not some unbelievably vanishingly rare thing,” says study leader David Lynch from University College London, UK.
An early and accurate diagnosis is extremely important. It allows people to plan their lives with a disabling and ultimately fatal condition, and lets them access support – including future medications, the first one of which could soon be available.
A commonly misdiagnosed disease
Alexander disease is a leukodystrophy, one of a group of conditions that affect the brain’s communication network. It typically affects young children, with much fewer people developing the condition later in life. There’s currently no cure for Alexander disease, and it tends to get worse over time: people can eventually lose their ability to walk, talk and swallow.
The early symptoms of Alexander disease in adults are varied, ranging from memory to movement problems, and can mimic those of completely unrelated conditions. “A lot of adult leukodystrophy patients are [initially] diagnosed with depression and anxiety,” says Karen Harrison, director of support at Alex, The Leukodystrophy Charity.
One of the reasons symptoms are so often misinterpreted is because “the current thinking across the medical profession is that this is a really, really rare disease”, says software developer Nathan. He was diagnosed two years after he started struggling with fatigue and leg pain while playing golf.
Not that rare
Alexander disease is caused by differences in one particular gene. These mutations can be inherited, though more often they happen spontaneously at the time of conception.
Genetic data from UK Biobank participants suggests as many as 1 in 15,000 in the UK may carry the Alexander-disease gene mutation.
Genetic data from all 500,000 UK Biobank participants revealed that the Alexander-disease gene was surprisingly common for something labelled as an ultra-rare disease. This suggests that as many as 1 in 15,000 people in the UK may carry the mutation – much more than the previous estimate of one in almost three million.
“The leading theory is that perhaps Alexander-disease mutations don’t always lead to Alexander disease,” Lynch says. It’s also possible that some cases are being misdiagnosed or remain undiagnosed, he adds.
“I think that the three elements are interconnected with each other,” says Tiziana Bachetti, a specialist in Alexander disease at the IRCCS Ospedale Policlinico San Martino in Genova, Italy.
The first drug against Alexander disease
The fact that having an Alexander-disease mutation doesn’t necessarily lead to the condition might help parents with the condition who worry that they passed it on to their children.
“Even with individuals in the same family who all have the same mutation, some may have childhood-onset, some may have adult-onset,” says Lynch. Some research results hint at certain versions of the Alexander-disease mutation that only fully ‘activate’ later in life, says Bachetti.
Saying that [Alexander disease] may not be as rare as previously considered will also get drug companies to be a lot more interested.
Nathan, software developer and Alexander disease patient
There’s a lot of excitement about the very first Alexander-disease drug that improved patients’ mobility in early tests. The therapy could soon be available in US clinics – and eventually elsewhere. “Saying that [Alexander disease] may not be as rare as previously considered will also get drug companies to be a lot more interested,” Nathan points out.