A Strict Regimen For Staying Alive Protein Disorder More Common Among Mennonites

Posted: September 25, 1988

For little Idann Hoover, breakfast, lunch and dinner are the same every day: a cool, milklike synthetic drink and a small serving of cereal, vegetables or noodles.

No steak, seafood or chicken - none of the dishes most people take for granted. The protein in meats and other foods would kill her.

"If I like something, I think it would be nice for Idann to eat it," said her mother, Annie. "But she can't. It would make her sick."

Idann, 4, of Leola, Lancaster County, is suffering from a rare genetic disorder that afflicts one in 225,000 newborns around the world - and one in 176 babies in Mennonite communities, where intermarriage is common.

She and at least 27 other children and young adults across the state have inherited Maple Syrup Urine Disease and cannot metabolize certain amino acids in protein.

The little-known condition, which received its name from the odor it gives the urine, usually results in early death, sometimes at birth because some cases are undetected or from a simple infection or virus in later life. In either case, its victims succumb to a buildup of toxins in the blood and tissues that ultimately causes the brain to swell.

Pennsylvania, because of its large concentration of Mennonites, has more reported MSUD cases than other states, indeed, more than any other nation, and Philadelphia has become the center for treatment, according to medical experts.

The commonwealth, however, does not require screening for the disease at birth - a step 22 other states have taken so that MSUD patients can be treated before serious brain damage takes place, the experts said.

Twenty Mennonites, including Idann, and six non-Mennonites undergo periodic checks at Children's Hospital of Philadelphia and St. Christopher's Hospital for Children, which have the largest MSUD clinics in the world, according to doctors at those institutions. And with no cure, those afflicted must live on special, restricted diets and, during acute attacks, face painful dialysis to cleanse their blood of the toxins.

"It's a terrible disease," said Dr. Iraj Rezvani, who treats MSUD patients at St. Christopher's. " . . . And the cure may be many years off."

Dr. Gerard T. Berry, who treats MSUD patients at Children's Hospital, added: "We still don't know what life holds for these children as they become older." The oldest patient is in her 20s.

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Dale Eby caught a virus last month - the kind most people recover from in a few days.

But nine days after the first symptoms appeared, he died Aug. 23 at Children's Hospital.

His body, in trying to throw off the sickness, burned up its own protein - in effect, killing him with the buildup of toxic byproducts - because Dale, 6, a Mennonite from Ephrata, Lancaster County, had MSUD.

He was buried in a cemetery next to the Muddy Creek Old Order Mennonite Church, nestled in the rolling farmland near Reamstown, Lancaster County.

"At the graveyard, I saw the tombstones of many young children," said Dr. Marc Yudkoff, who treated Dale at Children's Hospital. "It was very striking. You can't help but wonder if those deaths were attributable to MSUD."

The disease was first identified in 1954 but was claiming the lives of newborns long before doctors recognized it.

It was probably carried into the country by one or more early Mennonite settlers who came to America in the 1700s and began farms in what is now Lancaster County, according to Joyce Brubacher, 46, a Goshen, Ind., Mennonite who has done extensive genealogical studies.

Brubacher said most Mennonites could trace their ancestry back to some of those settlers: Henry Weaver and his wife, Maudlin Kendig; Hans Wenger and his wife, Anna Sherk; Andrew Martin; Abraham Brubacher, and Glause Zimmerman and at least one of his three sons.

"We can trace back to just about all of them because there was so much intermarriage," she said. "There is no way to pinpoint the one who had the damaged gene to begin with. That person probably would have lived in Europe earlier."

Rezvani, who also has researched Mennonite genealogy, said the gene remained in the community's gene pool because of the intermarriage, increasing the likelihood that both parents would be carriers, which is necessary to have children with the disease.

"In the general population, that gene would be diluted," he said. "So, if you were a carrier, you probably wouldn't find the person with the other half. When you have intermarriages, that's when you get the manifestation of the disease."

Dr. Angelo DiGeorge, a St. Christopher's Hospital physician who diagnosed the first case of the disorder in the state in 1968, said the high incidence of MSUD across Pennsylvania had made the state "the MSUD capital of the world."

Brubacher, whose 18-year-old daughter, Shayla, has the disorder, said Mennonite cases of the disease had been reported in Missouri and Canada.

There are about 100 people with MSUD in the United States, and many more cases have been diagnosed around the world.

"The disease is in many ethnic groups today - not just in the Mennonites," Brubacher said. "It's something everyone should be concerned about because it's everywhere."

Annie Hoover can always tell when something is wrong.

Idann "gets more irritable and fussy," she said. "Then, she'll get tired and lethargic."

Hoover, 40, and other parents of MSUD victims have to watch their children carefully while maintaining a delicate dietary balance.

"I have to always remember to have something for her (to eat)," she said. ''Whenever I can, I try to cook a certain vegetable that she can have along with the whole family."

Unlike most people, Idann lacks the enzyme to metabolize the so-called branched-chain amino acids in protein. Proteins are made up of 20 amino acids; nine of them are essential for proper nutrition and three of the nine are the branched-chain type - leucine, isoleucine and valine.

"Normally, the first step in their degradation is to be converted into ketoacids," said Berry.

MSUD patients "cannot properly break down ketoacids because of the missing enzyme, so (they) build up in the blood and body tissues."

Rezvani said MSUD patients need some branched-chain amino acids to survive ''but can't handle the excess" like other people. "You have to ration it so they don't get too much, just enough," he said.

Berry said the ketoacids apparently damaged brain cells and tissues but ''how they do it . . . is not clear."

Berry said he had recently used an experimental intravenous solution to help lower the poisonous levels of these branched-chain amino acids and ketoacids and had had success with two patients.

Kay Larson has turned the rationing into a science. She measures out every food serving, right down to the number of potato chips on the plate.

"Six of them have 33 milligrams of leucine," she said.

After long hours of studying nutritional guides and preparing special menus, she knows the exact dietary needs of her adopted daughter, Maritsa, 11, a non-Mennonite.

"I have a stack of books on food, listing its composition, protein and amount of amino acids," Larson said. "They've helped me make up menus."

Larson, 46, of Easton, said she monitors the amount of leucine Maritsa receives in every meal. "It's not easy," she said. "I know she can have 1,400 to 1,500 milligrams of leucine a day if she's healthy, 500 to 800 if she's got a fever and zero to 300 if she's really sick."

Fruit, french fries and other low-protein vegetables, pasta and bread can be part of the diet of MSUD patients. But the mainstay is the formula, which comes as a powder or already mixed as a milklike liquid, with or without branched-chain amino acids.

Patients, depending on their age, may get their nutritional requirements

from the formula or from a combination of formula and other foods. Maritsa's formula, for example, does not contain branched-chain amino acids.

"At church fellowship dinners, the table is groaning with food," Larson said. "There's a bounty of food and not one single thing suitable for her.

"So much of our society is built on food and the sharing of food. You don't realize it until you have someone with a restrictive diet. Maritsa wants to share but everything she has is measured out."

Most MSUD victims, such as Mennonite Marlene Zimmerman, have the classic form of the disease, requiring the limited protein intake.

Her mother, Verna Zimmerman, 38, of Ephrata, Lancaster County, said Marlene, 7, had been tempted to ask for foods that were not part of her diet. The youngster was diagnosed with the disease three weeks after birth and was left physically handicapped and mildly retarded.

"Some meals we eat just like her," Zimmerman said. "Other meals she has to learn there are some things she can't eat."

Another Mennonite, Mary Kathryn Martin, 37, of New Holland, Lancaster County, also has to keep her child, Keith, 10, on a strict diet.

"It hurts, especially at picnics," Martin said. "But you can't go off. If you do, it can show up the next day or it can show up in two hours."

But fellowship with the families of other MSUD victims helps, said Martin.

"We develop a special bond, closer than some in our family," she said. ''We share the uncertainty."

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