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Maryland Youth May Help Pioneer Cure for Gaucher's Disease

December 11, 1987|DANIEL Q. HANEY | Science Writer and Associated Press

POTOMAC, Md. — Brian Berman, age 3, was 33 inches tall and 25 inches around. His belly was so swollen that his mother said he looked like a cabbage with legs.

Brian was a loser in the genetic lottery, the game every person-to-be plays at conception.

Because he descends from Eastern European Jews, the odds were 1 in 676 that he would be born with an obscure illness called Gaucher's disease. But because his parents both carried one recessive gene for this disease, the odds were 1 in 4 that he would get it.

And he did. Like 15,000 to 20,000 other Americans, he inherited two bad versions of a gene that helps oversee one of the body's arcane housekeeping chores, cleaning up worn-out blood cells.

In another way, however, he was unusually lucky. Brian happened to be a patient at the federal government's health research complex in nearby Bethesda at just the right moment. Researchers working there under Dr. Roscoe O. Brady had been trying for 30 years to isolate, purify and modify the enzyme that his body lacked. After several false starts, they hoped they had hit at last upon the right formula.

On Dec. 22, 1983, just three weeks before he was scheduled to have his spleen removed, Brian received an injection of modified glucocerebrosidase. It worked. Or so it appeared.

Energetic Third-Grader

Now, at age 7, Brian still gets the shots every Thursday, and he still shows some signs of the disease. His belly is a bit larger than normal. But he is clearly a happy, bright, energetic third-grader.

He is also a sort of medical pioneer, for he is the only person to receive regular therapy with what, some experts believe, will prove to be the first successful treatment for Gaucher's disease.

Other researchers are not so sure. They point out that Brian is the only patient who has clearly benefited from the treatment, and it has failed in several others.

But to Brian's mother, Robin, herself a physician, the meaning is clear: "I feel it's a miracle."

To Brady, the boy's improvement--and the potential it may hold for others--are the rewards of a career largely spent studying one rare disease.

"It certainly is gratifying," he says. "It took a long time, didn't it? This started in 1957. Thirty years."

The ordeal for Brian and his parents began in the spring of 1983 when Mrs. Berman glanced at her son while he was napping.

"I noticed that Brian's belly looked very big to me," she remembers. She had already brought this up with to two other doctors, who assured her nothing was wrong. This time, though, she asked a surgeon who lived nearby to examine her boy. "He said, 'There's a big mass in there."'

His spleen was enlarged. At first, doctors suspected leukemia. But finally the diagnosis came back: Gaucher's disease.

"I frantically racked my mind," Mrs. Berman said. "We had about 10 minutes on it in medical school. I couldn't remember what it was all about."

She quickly learned that some of the world's experts were down the road at the National Institute of Neurological and Communicative Disorders and Stroke, where Brady is chief of the Developmental and Metabolic Neurology Branch.

She approached Dr. John A. Barranger, then the clinical director in Brady's group. "I asked him if he would let me work gratis. I didn't want to be paid. I wanted to learn everything I could about this disease." She closed her family practice and began seeing Gaucher's patients.

Lipid Storage Disorders

She learned that Gaucher's disease is one of a handful of so-called lipid storage disorders, including Tay-Sachs disease, that are most common among Ashkenazi Jews, those who emigrated from Eastern Europe.

When blood cells wear out, the body recycles them by breaking down their building materials, including a fatty substance called glucocerebroside. To do this, it makes a specialized enzyme called glucocerebrosidase. However, in Gaucher's victims, the gene that makes this enzyme is defective. As a result, glucocerebroside builds up in their bodies.

It tends to collect in cells called macrophages in the liver, bone marrow and spleen. The consequences vary greatly from person to person. Some die in childhood, while others notice no symptoms until late in life.

Often though, they become severely anemic. Their blood doesn't clot properly, so they bleed at the slightest injury. Their livers and spleens are enlarged. Over time, their bones grow brittle and break easily. They may suffer deep bone pain.

Removing the spleen can help temporarily. But this may also increase susceptibility to infections, and some think it speeds bone damage. Otherwise, little can be done to control the disease.

During that fall, there was "an aura of expectation" in Brady's lab as researchers worked on the enzyme, Mrs. Berman remembers. But meanwhile, Brian's condition quickly worsened.

"He started to get very sick," she said. "He went down hill so that he couldn't walk up stairs. He looked like a cabbage with legs. He had a huge belly and wasting extremities."

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