An international consortium of scientists, led jointly by researchers at UCL’s Institute of Neurology and Duke University, USA, has identified the specific genetic mutation that causes Alternating Hemiplegia, a rare neurological condition affecting an estimated one child in every million. Using the newest genetic technology, next-generation sequencing, the study published in Nature Genetics, showed that de novo mutations in the gene ATP1A3 cause the condition (de novo mutations are genetic mutations not present in the parents’ genes).
Alternating Hemiplegia is characterised by onset in infancy or childhood of episodes of weakness of one side of the body; later in the course of the disease, both sides may be affected at the same time. The weakness typically gets better, but reoccurs in the next episode. The symptoms can vary from child to child and from day to day. For many affected individuals, other symptoms also occur, including speech, swallowing, and behavioural problems. Intellectual difficulties, movement disorders and epilepsy can also occur. The variety of symptoms and signs, and their variation over time, can lead to delays in diagnosis, multiple tests and investigations, and sometimes use of inappropriate treatments. So far, no definitive diagnostic test has been available, and a rational understanding of the disease has not been possible.
This study paves the way for future rational treatments for the condition, through a better understanding of underlying disease mechanisms. Whilst this will take some time, the discovery will have a direct impact in enabling more rapid, specific diagnosis of the condition, preventing unnecessary tests and misdirected treatment.
Jill Bailey, from the UK Alternating Hemiplegia Support Group said: “The discovery of the gene has given hope to parents whose lives are dominated by alternating hemiplegia. Our hope is that in the future a drug will be found that stops our children suffering these awful hemiplegic attacks. Our hope is that more money will be available for further research. Our hope is that our children will have a better life.”
The research was jointly led by Professor Sanjay Sisodiya at UCL and Professors David Goldstein and Mohamed Mikati at Duke University, and is published in Nature Genetics. The study was funded by several sources; Professor Sisodiya’s funding was from The Wellcome Trust.
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