Liver transplants seem to be curing about a dozen children of a rare disease so unforgiving that the slightest dietary misstep can prove brain-damaging or even fatal.
Now instead of a life of fear with every bite of a strict low-protein diet (search), these patients with maple syrup urine disease eat ice cream, hamburgers and other normal kid fare.
And doctors are studying whether the transplants don't just avert future problems but also might help children who already had suffered some brain damage to get a little better.
"Subjectively we're noting things like improved attention span, better speech, areas we are thrilled that are occurring," says Dr. George Mazariegos of Children's Hospital of Pittsburgh, who is about to publish in a medical journal the anxiously awaited first results of this dramatic new approach to treating the genetic disease.
As the mother of his first patient puts it: "It's a new life for us," says Susan Jasin of Alpharetta, Ga., whose son Jakob, now 5, underwent the transplant in May 2004.
Maple syrup urine disease (search), named for the telltale symptom of sweet-smelling urine, occurs in about one in 225,000 births. Patients' bodies can't process three amino acids found in protein — leucine (search), isoleucine (search) and valine (search). Those amino acids can build up to toxic levels, causing mental retardation, physical disabilities from neurologic damage, and even death.
To survive, patients are put on a lifelong diet super-low in protein; many patients' primary nourishment is a special liquid formula. Because some protein is in most foods, restrictions on other fare go beyond no meat or dairy products. Jakob, for instance, liked potatoes but his mother carried a scale to measure precisely the handful of french fries his body could tolerate.
Diet aside, even a minor illness that causes children not to eat on schedule can send them into seizures as their bodies break down stored protein.
Improved newborn screening is allowing treatment to start earlier, saving lives. But few patients reach adulthood without some neurologic delay or worse, says Mazariegos, who described his team's first 13 transplants at a recent pediatricians' meeting.
All the patients began eating a regular diet within days of surgery, and their bodies are normally processing protein, Mazariegos reports. Five had mild symptoms of organ rejection, controlled with medication.
Any age after 1 seems OK to operate, he says. The median age of his patients is 6; the youngest was 1 1/2 and the oldest 20.
That a transplant might help was a surprise, discovered when an 8-year-old with MSUD received one after a vitamin A overdose destroyed her liver. Her amino acid levels normalized within hours of the 1997 transplant, and she's been fine since.
A new liver doesn't rid the body of the genetic defect, but it seems to carry enough of a protein-digesting enzyme to counter the defect.
Yet doctors initially were reluctant to offer elective liver transplants for MSUD, citing the grueling operation's risks and the threat of organ rejection. Moreover, scarce donated livers generally are reserved for people with no other option — and the fasting typically required before a transplant itself could harm MSUD patients. Indeed, one early attempt failed.
But as pediatric liver transplants in general improved — including the need for fewer immune-suppressing drugs to prevent rejection — the Pittsburgh team heeded parents' request to try again, designing a method to minimize metabolic risks.
A few other hospitals also offer MSUD liver transplants. The University of California, San Diego, even performed a so-called domino transplant, giving a cadaver liver to a 25-year-old MSUD patient and giving his original liver — which would work in someone who doesn't have the genetic disease — to someone with liver cancer.
Some cases of MSUD are milder than others, and many patients seem to do fine with the diet. And there is no long-term data yet on how these children will fare.
Jasin pushed for the transplant because even strictly following the diet, Jakob was hospitalized with brain swelling during metabolic crises, a toll she feared would eventually result in serious damage.
"It was the hardest thing I've ever gone through," she says of the operation. But Jakob today is a healthy, pepperoni pizza-loving kindergartner.