Rare Illness May Be Key to Secrets of Cancer

A mysterious and rare genetic disorder discovered by accident during routine physicals of Los Angeles schoolchildren may provide clues to understanding cancer and immune system deficiencies, researchers say.

The childhood disorder, often misdiagnosed as cerebral palsy, is known by the tongue-twisting name of ataxia-telangiectasia, or more simply as AT.

It is an inherited trait, and studies show that as many as one in every 100 people may be carriers of the defective gene although the disease is believed to occur in only one of every 50,000 births.

“The disease appears between 1 and 2 years of age in otherwise normal-appearing children,” said Dr. Richard Gatti, a UCLA research pathologist.

“They begin to walk at a normal age but become more clumsy with time and it is often after the onset of excessive clumsiness that it becomes obvious to parents that there is a neurological basis for the problem.”

Maladies Seemingly Unrelated

Carriers do not develop the disease, but when two carriers have children there are increased chances that the offspring will develop the disorder, which manifests itself in a number of seemingly unrelated maladies.

“Early in this disease there is a tendency to misdiagnose it as cerebral palsy, but it is clear that it is not when it continues,” Gatti said.

Aside from the clumsy gait that develops by age 2, AT victims usually must be confined to a wheelchair by age 10 and many also develop heart malfunctions and a significant loss of cells in the brain’s cerebellum--a symptom similar to that found in alcoholics.

Gatti, who has been studying the disease for 15 years, said AT was first described in the late 1950s by Dr. Elena Boder, a Los Angeles physician who identified the disorder in six schoolchildren during physicals.

Accurate Predictions

Later observations led to the identification of AT in children across the country.

There is no known cure or prenatal method of testing for the fatal disorder.

The UCLA research team is studying an Amish family group in Pennsylvania with hopes of devising an accurate way of predicting who will develop the disease and ultimately finding the chromosome that carries the defective gene.

Once they locate the key chromosome, Gatti said, scientists will have a more accurate way to predict who is at risk to develop cancer.

The UCLA study indicates that a third of all AT victims develop cancer, despite an average life expectancy of only 20 to 25.

“These children have a deficient immunity,” Gatti said, “and that correlates with the general observation that all children with immune deficiency diseases have a striking increase in the incidence of cancer--about 1,000 times more frequent than the general population.

He said 80% of these cancers are lymphoma or leukemia, although AT victims also have developed cancers of the stomach, breast, pancreas, brain and liver.

The researchers have also found that even carriers of the defective gene are more susceptible to cancer than the general population.

“The carriers are not as normal as they appear,” Gatti said. “They have a sixfold increase of susceptibility to cancer, and the female carriers may be especially susceptible to breast cancer.”

Scientists also believe that victims of AT are extremely sensitive to radiation because those receiving radiotherapy for cancer developed burns characteristic of much higher doses.

Gatti said the tendency to burn and develop tumors may be linked to the discovery that the chromosomes of AT victims break apart easily and are prone to rearrange in mismatched fashion.

Radiation Affects Chromosomes

He said radiation also causes chromosomes to break apart in people without the disorder, but their genetic material invariably finds its way back to the proper position.

Gatti said the genetic patterns follow the laws discovered by the 19th-Century Austrian monk Gregor Mendel. For example, AT affects only about a fourth of the children born to carrier parents, while half of such children would be carriers and the other fourth would be normal.

“These children seem to represent an experiment of nature, a Rosetta stone for explaining the relationship between cancer susceptibility and a genetic defect that translates into that susceptibility,” Gatti explained.

The Amish family being used for the study was chosen because people with AT have been identified in four different branches that have members “all tracing their ancestry to a single individual born in 1750,” Gatti said.