Parkinson's misdiagnosed

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Parkinson's misdiagnosed

By Helen Pearson, the Nature

January 28, 2004

A mutation of the X chromosome causes FXTAS

New condition explains some movement disorders and dementia.
Some patients diagnosed with Parkinson's disease or the wear and tear of ageing may actually be suffering from a recently discovered brain disease, doctors say.
The disease, called FXTAS, strikes around 1 in 3,000 men over the age of 50, according to Paul Hagerman of the University of California , Davis , and his colleagues. It causes gradually worsening symptoms of tremors, difficulty in initiating movement and memory loss.

Hagerman suspects that as many as 10% of patients diagnosed with atypical Parkinson's, in which patients tremble when they move, might actually have FXTAS. He hopes that doctors will now screen these patients for FXTAS with a simple genetic test.

Larger studies must be done before doctors can be sure about how common FXTAS really is, cautions Stephen Warren, who studies the disorder at Emory University in Atlanta , Georgia . But, he says, "I'd buy the argument that many of these patients are diagnosed with something else."

Common people

Researchers have known about FXTAS for a few years. It is caused by a mutation in a brain-growth gene called FMR1, which sits on the X chromosome. One section of the gene repeats itself over and over again, like a stutter.

In people with 200 of these repeats, the FMR1 gene is switched off. They develop fragile-X syndrome, the most common form of inherited mental retardation, which affects roughly 1 in 3,600 boys, and affects girls to a milder extent.

A further 1 in 800 people carry between 55 and 200 genetic repeats, called a premutation. Once thought to be harmless, researchers have since discovered that the premutation boosts the activity of the FMR1 gene which kills off nerve cells, leading to FXTAS.

Hagerman assessed 99 people who carry premutations, and found that around one-third of those over the age of 50 showed signs of FXTAS. Women may escape the disease, probably because they have another X chromosome to compensate for the defective one.

Mixed bag

Doctors suspect that Parkinson's and other coordination disorders, called ataxias, are actually ragbags of diseases lumped together because of similar symptoms. They sometimes unearth genes that can explain a handful of such cases. FXTAS seems to be relatively widespread for a disease caused by a single gene.

There are few data yet on whether the prognosis for FXTAS is better than that for Parkinson's, says team member Elizabeth Berry-Kravis of Rush University in Chicago . But a correct diagnosis might prevent the prescription of inappropriate drugs; some patients in the study had even had unnecessary brain surgery thanks to the misdiagnosis.

As researchers understand what causes FXTAS, they can also start working on drugs tailored to treat it, Berry-Kravis says. They have a head start, she adds, because a lot is already known about the gene.