Scientists in Dublin and Paris have shed light on a very rare condition affecting children -  alternating hemiplegia of childhood (AHC).

This condition can lead to repeated paralysis of one side of the body and sometimes affects both sides at once. It usually begins to affect children before they reach 18 months of age. To date, only one causative gene has been identified.

However, scientists at Trinity College Dublin and the Institute Imagine at Necker Hospital in Paris have now identified a second gene (CLDN5) as being responsible for the condition in two unrelated cases of AHC in France.

The protein product of this gene, claudin-5, is critical for maintaining the integrity of the blood-brain barrier (BBB). The scientists found that the mutated form of the protein turns the barrier into a channel that is selective for negatively charged ions. As such, the ionic composition of the brain is likely shifted in these children and this is a key driver of the condition.

“The identity of these de novo mutations in unrelated children suggests that the barrier is turning into a channel. This is exciting on numerous levels as it is the first report of the BBB turning into a channel, but it also sheds light on the devastating pathology of AHC, which may assist in clinical management of patients with this mutation,” explained Dr Matthew Campbell, associate professor of genetics in TCD’s School of Genetics and Microbiology.

As this is the first report of the human BBB becoming a channel, the researchers pointed out that this may lead to avenues for drug delivery that have never been explored. This will now form the basis of the next steps of the project.

“We are delighted this work has progressed so quickly and our groups have been able to work very closely to identify the cause of this condition. Studies like this will benefit families and clinicians immensely in the years to come,” commented Prof Arnold Munnich of the Institute Imagine in Paris.

The research involved a multidisciplinary team of geneticists, neurologists and radiologists from Ireland and France. It was supported by Science Foundation Ireland (SFI), FutureNeuro, the Japanese Society for the Promotion of Science (JSPS) and the European Research Council (ERC).

It has been published in the journal Brain and can be viewed here.