Press Release

Department of Human Genetics
Eccles Institute of Human Genetics
University of Utah

RELEASE DATE: 3 Mar. 2000

contact:
Connie Barth -- (801) 585-6135
Ying-Hui Fu, Ph.D., 801-581-3993
Louis Ptácek, M.D., 801-581-3993

Contacts at the National Multiple Sclerosis Society:
Arney Rosenblat, Director of Communications, 212-476-0436
Holly Reynolds, Public Relations Coordinator, Utah State Chapter, 801-493-0113

SALT LAKE CITY, Utah -- The gene causing Adult-onset Autosomal Dominant Leukodystrophy (ADLD) has been localized to chromosome 5 by University of Utah scientists. This may provide a clue to the mysteries causing other similar neurodegenerative diseases such as multiple sclerosis. Findings of the study are reported in the March 22, 2000 issue of the journal Human Molecular Genetics.

ADLD and multiple sclerosis (MS) both result from degeneration of a nerve cell insulator, but the cause of the degeneration is unknown. Studies of the gene causing ADLD may provide some answers to these questions for MS as well as ADLD. "While ADLD is a rare disease, understanding ADLD may offer insight into other diseases such as multiple sclerosis. This is an unusual and special opportunity to study a disease that resembles MS, which affects over a third of a million Americans," says Ying-Hui Fu, Ph.D., a researcher at the Eccles Institute of Human Genetics and lead author of the study.

Both diseases are part of a group of neurodegenerative illnesses that cause progressive loss of movement. ADLD patients are unique because they experience some unusual symptoms fairly early in disease progression (ages 30-45), including male impotence, decreased sweating, bowel/bladder dysfunction, and a drop in blood pressure when standing up. Loss of fine motor skills typically begins several years later and progresses to complete loss of voluntary movement and death after 20-30 years.

Due to ADLD's clinical similarity to some forms of MS, patients are often misdiagnosed with MS; 20 family members in the ADLD study were misdiagnosed before doctors became aware of ADLD and brain imaging techniques were available. However, genetics appear to play a larger role in ADLD than MS because fifty percent of the children born to a person with ADLD will also develop the disorder, while the role of genes in MS is not clear.

The gene causing ADLD is likely involved in the production and maintenance of myelin, a sheath comprised of lipids and proteins, which works as an insulator for nerve cells. The finding is significant because it will provide "an insight into a novel mechanism of myelin metabolism," according to Louis Ptácek, M.D., an investigator with the Howard Hughes Medical Institute at the Eccles Institute, and study participant. "When this insulator is improperly produced or installed on nerve cells, it slows the rate at which nerve signals travel between the brain and other parts of our bodies. When the signals travel too slowly, we lose muscle coordination and other neurological functions such as sensation and vision," says Ptácek. Patients with ADLD or the primary progressive form of MS experience a slow loss of movement control as the myelin degeneration becomes worse until they have a total loss of control.

Since ADLD is produced by a mutation in a single gene rather than a combination of several genes and environmental factors (which is likely the case with MS), it presents a clearer target for researching its genetic cause. "We hope that studying this rare myelin disease (ADLD) will increase understanding of causes and treatments for common disorders like MS," says Fu.

Researchers from the University of Utah School of Medicine, Albany Medical College, Neurology of Arkansas, Johns Hopkins University, and University of Louisville, Kentucky, contributed to the study. This work was funded in part by the Howard Hughes Medical Institute, the National Institute of Neurological Disorders and Stroke, the National Multiple Sclerosis Society, and the National Center for Research Resources.