TUESDAY, Jan. 27, 2004 (HealthDayNews) -- Doctors may frequently be confusing Parkinson's disease, Alzheimer's and similar age-related neurological ailments with the symptoms of a recently discovered genetic disorder that's surprisingly common yet unfamiliar to most physicians.
The illness is called fragile X-associated tremor/ataxia syndrome, or FXTAS (pronounced fax-tass). It typically affects men over age 50, causing tremors, balance problems and dementia, which all progressively worsen over time, much like Parkinson's and related conditions. People afflicted by the genetic flaw appear normal through childhood and much of their adult life.
FXTAS is closely related to fragile X syndrome, the leading cause of inherited mental retardation.
Fragile X occurs when cells in the body don't product a protein produced by the fragile X mental retardation 1 gene (FMR1). Men with fragile X syndrome suffer from mental and motor impairment, autism, elongated faces, enlarged ears and testes, and connective tissue problems. In women, retardation may be accompanied by premature menopause in about 25 percent of people.
Previous studies have found that about one in 259 women and one in 813 men in the United States are born with oversized versions of FMR1. The gene is bulged by stretches of repeating DNA, called "premutation expansions," whhich cause cells to think they're not producing enough FMR1.
Rather than cause retardation, this error often leads to high intelligence and achievement, at least in early and mid-life, says Dr. Randi Hagerman, a fragile X expert at the University of California at Davis and a co-author of the study.
"Generally, these individuals are very smart and very productive," Hagerman says. But starting in their 50s and beyond, she adds, they begin to show signs of brain damage -- the result, apparently, of tiny pearl-like protein clusters that accumulate in their neurons.
Men inherit premutation expansions from their mothers and pass them along to their daughters, all of whom have the abnormal gene. The expansion can grow in size when the daughters pass it along to their own offspring.
Although women have premutation expansions more often than men, they usually are protected from illness by their second X chromosome, whose normal FMR1 gene can override the abnormal version.
Robert Miller, executive director of the National Fragile X Association in San Francisco, says roughly one in 3,600 men and one in 4,000 to 6,000 women have fragile X syndrome. Many are undiagnosed. The latest findings should help doctors identify patients not only with FXTAS but with fragile X syndrome as well, Miller says.
"It's going to go both ways," Miller says. Neurologists who diagnose FXTAS in an older man should look for fragile X mutations in his daughters. Similarly, a pediatrician who diagnoses fragile X in a child should ask that child's parents about the health of his or her grandfathers.
Most premutation expansions were thought previously to have no health consequences in the men whose genes contained them. However, the latest study, reported in the Jan. 28 issue of the Journal of the American Medical Association, changes that view.
In the latest research, Hagerman and her colleagues studied 192 people (99 men and 93 women) with relatives known to have fragile X syndrome. The scientists looked for tremors and motor woes in men with gene expansions, as detected by a blood test that reads DNA.
The 40 men with gene expansions were 13 times more likely than those with normal copies of FMR1 to have tremors and trouble walking, the researchers say. These symptoms grew more common with age, and three-quarters of men 80 or older had them.
Men with gene expansions also were more likely to score poorly on neurological exams than unaffected men. Women with the gene expansions didn't seem to be prone to FXTAS.
The study suggests that as many as 30 percent of men with premutation expansions of their fragile X protein gene, or nearly one in 3,000 men, may develop FXTAS later in life.
So far, men with FXTAS haven't been properly diagnosed. "For all of the patients that we've discovered, doctors have diagnosed them with different disorders. But it's really FXTAS that's involved here," says Hagerman, who is director of UC Davis' Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute for brain studies.
"We hope that this [study] will lead to the identification of this problem much more commonly," she adds.
Some patients with FXTAS do respond to drug treatments, Hagerman says, including medications for Parkinson's symptoms, anxiety and depression, and cognitive problems.