Drug gives PKU sufferers a chance to eat protein

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For much of her life, 12-year-old Norah Marsh of Bellevue missed out on many of the pleasures of eating. While her schoolmates enjoyed pizza or hamburgers at lunch, for example, Norah might eat a salad and a grape jelly and Cool Whip sandwich. Sadly, she said, "I couldn't have ice cream when my team won a basketball game."

That's because she was born with PKU, or phenylketonuria, a genetic disease that leaves the patient unable to process protein because of a deficiency of the enzyme needed to break it down. That enzyme is called PAH, short for phenylalanine hydroxylase. Without it, a building block of protein called phenylalanine, or Phe, builds up to toxic levels that eventually can cause brain damage, including severe retardation in undiagnosed infants.

Until last year, the only way of controlling PKU was through an extremely protein-restricted diet and sometimes foul-smelling dietary supplements.

Now, after three trials at multiple North American and European medical centers, including Children's Hospital of Pittsburgh of UPMC, the federal government has approved a new drug called Kuvan that helps up to 45 percent of all PKU patients live a more normal life. It works best in patients who, like Norah, start out with intermediate levels of Phe.

"What the Kuvan does in individuals who respond is help stabilize the abnormal enzyme," said Dr. Jerry Vockley, chief of Children's Hospital division of medical genetics and lead scientist of the hospital's Kuvan study.

"The whole goal is to keep the Phe levels in normal range."

PKU patients are not born with retardation because the mother's placenta cleans the baby's blood in utero. "It isn't until the baby is born that the phenylalanine starts to accumulate ... [and] over time the accumulation is toxic to the brain. There's a critical window for treatment," Dr. Vockley said.

For that reason, Pennsylvania has required newborn screening for PKU since the late 1960s.

"Babies who were born before then are very severely retarded with bad movement disorders, writhing and restlessness," Dr. Vockley said. They are now in their 40s or older.

The low-protein diet has worked well at maintaining safe Phe levels -- as long as patients stayed the course. But its rigidity often led to rebellion, and that could lead to a wide variety of brain damage.

"If you have a 4- or 5-year-old whose level is uncontrollable, learning deficits can occur," Dr. Vockley said. "When older kids, who are otherwise well, come off their diets, you might have something as specific as [attention deficit disorder]. With adults, if you come off you get into the problem of a loss of IQ points and an increase in personality problems. It's usually described as a lack of 'executive function.' They don't organize well. They have a hard time holding jobs and the problems associated with that.

"You can have an increase of psychiatric disorders ... mostly affective disorders, major and minor depression," he said.

Going on Kuvan would not correct brain damage already incurred, Dr. Vockley said. "Brain damage is irreversible. That's the reason the states started mandated screening."

Norah was easily controlled when she was younger, her mother, Jo Marsh said, even though she was allowed just 8 milligrams of Phe a day -- the equivalent of about a half cup of regular pasta.

But recently, her mother added, she became more independent and began eating forbidden foods.

"She was cheating left and right," Mrs. Marsh said.

"There was NOTHING to eat," Norah countered. For years she had survived on fruits and vegetables, only to develop allergies to the former. Her favorite food to sneak became chicken nuggets.

Thanks to Kuvan, Norah had the pleasure of answering the question "do you want white meat or dark meat" for the first time last Thanksgiving Day. Since then, shrimp and a double cheeseburger with bacon have become her favorite foods.

Pohla Smith can be reached at psmith@post-gazette.com or 412-263-1228.


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