A team of researchers, led by physicians at the UC Davis M.I.N.D Institute, have discovered a new, progressive neurological disorder that predominantly affects men over age 50 and results in tremors, balance problems and dementia that become increasingly more severe.
A significant but currently unknown number of adults with these tremor and balance problems are being diagnosed with Parkinson's disease, senile dementia and Alzheimer's disease when their condition may be accurately and easily identified with a standard DNA blood test ordered by their doctor. The discovery is published in the Jan. 28 issue of the Journal of the American Medical Association.
Known as fragile X-associated tremor/ ataxia syndrome, or FXTAS (pronounced fax-tass), the disorder affects older men who are carriers of a small mutation in the same gene that causes fragile X syndrome, the most common cause of inherited mental retardation. Nearly 1 in 800 men in the general population carries this premutation in the fragile X gene, and UC Davis research suggests that as many as 30 percent of carriers -- roughly 1 in 3,000 men -- may develop FXTAS later in life.
"FXTAS may be one of the most common causes of tremor and balance problems in the adult population, yet it is being misdiagnosed because neurologists who see adults with movement disorders are not aware that they need to look for a family history of fragile X in grandchildren or to check for the presence of the premutation in the fragile X gene," said Randi Hagerman, medical director of the UC Davis M.I.N.D. Institute.
Research studies also are under way to determine what medications and therapies best alleviate FXTAS-related problems.
Hagerman, a developmental and behavioral pediatrician who has specialized in the diagnosis, research and treatment of fragile X for more than 20 years, began looking for a connection between children and their grandfathers because the mothers of her fragile X patients were worried about their own fathers, who were falling down, becoming forgetful and experiencing other neurological problems. Hagerman, along with her husband Paul, a professor of biological chemistry at the School of Medicine and principal investigator of the study, led the team of researchers from the M.I.N.D. Institute, University of Colorado Health Sciences Center, and RUSH-Presbyterian-St. Luke's Medical Center.
Researchers looked at 192 individuals whose families belong to the Northern or Southern California Fragile X Associations. While only 17 percent of the men in their 50s had FXTAS, the percentage of individuals with tremors and balance problems increased with each decade of life, to 38 percent of men in their 60s, 47 percent of men in their 70s, and 75 percent of men in their 80s. The study also showed that the majority of older male carriers of the premutation will develop at least mild symptoms of FXTAS.
Initial signs of the disorder may include difficulty writing, using eating utensils, pouring water and walking. These initial symptoms progress over years or even decades, until carrying out many of the tasks of daily living and walking without assistance becomes difficult or impossible. Other features include short-term memory loss, anxiety, decreased sensation in the lower extremities to touch and vibration, lower-limb muscle weakness and parkinsonism.
The underlying cause of FXTAS is a change, or mutation, in the fragile X mental retardation 1 gene, or FMR1. Under normal conditions, this gene produces a protein that maintains the proper functioning of nerve cells in the brain. The gene causes both fragile X and FXTAS when a particular segment of DNA is repeated too many times. The average person has 30 such repeats in the FMR1 gene. When an individual has 200 or more of these repeats, the individual makes little or no FMR1 protein and has fragile X syndrome. With 55 to 200 repeats, an individual is considered a carrier of the premutation, which can lead to FXTAS later in life.