Winter 2001
Volume 14, Number 1

New Genes Make Spotting Ataxia a Sure Thing

"I can't run the dogs." That was Lee Anthony's first sign of anything amiss. Then came a dramatic loss of balance and difficulty in walking. Within five years, the former Air Force pilot needed an electric wheelchair. Anthony's neurologists at Hopkins diagnosed one type of spinocerebellar ataxia, an autosomal dominant disease that progressively destroys the cerebellum and leads to other brain or peripheral nervous system irregularities. "You can surely do something, can't you?" he asked neurologist Elizabeth O'Hearn. She replied, "We're working on it as fast as we can."

Each issue,Brainwaves will report on discoveries that've come about, in part, because someone was moved enough to support the research. When Anthony died last February from other causes, his wife Sally wasted no time starting the "Ataxia Research Fund" at Hopkins, some of which supports O'Hearn's work described here.

"A clinician's nightmare" is how one neurologist labels the spinocerebellar ataxias (SCAs), mostly dominant inherited diseases that rob patients of balance and ability to walk properly. Slight shifts in the onset or nature of symptoms have led neurologists to recognize different forms of the disorders, but, still, symptom overlap is great and diagnosis tricky.

Several years ago, however, says neurologist Elizabeth O'Hearn, M.D., "the technology got good enough to let us identify SCA genes. They then began to accumulate at a dizzying pace. We're now up to 17," she says. Recently, a Hopkins team of psychiatrists and neurologists, including Susan Holmes, Ph.D., Russell Margolis, M.D., and O'Hearn, uncovered yet another, called SCA 12.

Like many ataxia genes, SCA12 is marked by an unnatural repetition of three DNA bases. It codes for an overabundance of a specific phosphatase enzyme "though no one," O'Hearn says, "knows why that's a problem."

Identifying the gene, however, is a great help, not only because it gives patients the relief of a sure diagnosis, but also because it can predict the course of the disease.

SCA 12, for example, usually hits patients in their forties, beginning with tremor and progressing to gait problems, reduced movement and an inability to alternate movements normally. Problems moving the eyes and overblown reflexes are also common.

In other studies, Hopkins clinicians have confirmed anecdotal evidence of SCA's emotional and cognitive effects. "Patients tend to have trouble with executive abilities like planning ahead," says Brandt, "probably because of damaged pathways from the cerebellum to the frontal lobe."

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