Gene for disorder that paralyses legs

Led by researchers from the University of Michigan Health System scientists have found a gene for a rare leg-weakening nerve disease that slowly robs children of their ability to walk.

This finding opens the door to better diagnosis and treatment of the disorder, and to insights into other spinal cord problems. "This is a major step forward in our understanding of HSP's [hereditary spastic paraplegia] causes, and has already allowed us to provide diagnostic testing to a few patients," says John K. Fink, University of Michigan neurologist.

"We have been looking for HSP genes since 1993, and we are happy to have found, at last, the first one for a childhood form of the disease. Now, the search continues for the rest."

Mutations in the gene SPG3A, causing alterations in the newfound protein dubbed atlastin that it encodes, may be responsible for as many as 25% of childhood HSP cases, says Fink. Together with a test for spastin, a gene for an adult form of HSP, gene testing may lead to diagnosis for more than 50% of HSP.

The disease is insidious, and may begin as toe walking in early childhood; or subtle difficulty walking and occasional stumbling. But as nerves within the spinal cord break down, HSP can progress to a complete weakening of the legs, and, in some cases, to more severe problems.

Fink and his colleagues also see the gene as a key to understanding why people with HSP, spinal cord injuries, primary lateral sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease) all experience a progressive degeneration of certain nerve fibres in their spinal cords.