Unusual domino series of transplants able to save more lives

When two Maryland children got lifesaving liver transplants from deceased organ donors in January, the children's diseased livers were not discarded, as such organs usually are. Instead, they were donated to two Virginia adults in an unusual domino series of transplants at MedStar Georgetown University Hospital in Washington.

Their gift opened a whole new avenue of treatment for adults who might have otherwise died waiting for a liver transplant.

Children generally are not allowed to be organ donors because they are considered too young to make an informed decision about the medical risks involved. In this case, their livers had to be removed anyway, and science had recently determined that the disease that caused their livers to malfunction would not appear upon transplantation. Size also wasn't an issue because a transplanted liver grows to fit whatever body it's placed in.

Two weeks after the transplants, Jeremy Dick, a 49-year-old Alexandria, Va., technology consultant, met Quadejah Harris, the 14-year-old who gave Dick her liver and in turn got a new one as part of the organ donation chain. Dick's liver had failed due to an autoimmune disease.

“I like to help people,” said Quadejah as she sat in a wheelchair waiting to go home to Waldorf, Mc., after her complex surgery. “What's the point in wasting my liver when it can save someone else's life?”

The series of transplants got its start due to a rare childhood genetic condition called maple syrup urine disease. Named for the distinctive sweet odor of an affected infant's urine, the condition usually gets diagnosed within a day or two of birth due to widespread screening through a heel stick blood test that hospitals have been performing on newborns since the early 1990s.

About 2,000 Americans are living with maple syrup urine disease, which usually strikes in infancy and prevents cells in the liver and elsewhere from producing enzymes that break down certain amino acids in proteins. An accumulation of these amino acids can trigger swelling in the brain that leads to seizures, brain damage and death if babies aren't put on a strict low-protein diet. These attacks can occur unpredictably when a child's body is stressed by an infection, injury or other bump in life.

A liver transplant presents the only shot at a cure for the condition; children given healthy new livers can make enough of the needed enzymes, transplant surgeons discovered a decade ago.

And because adults without maple syrup urine disease produce enough of the enzymes in their other organs, getting a child's impaired liver is not a problem.

“It was initially a huge leap of faith when we started doing liver transplants in children with maple syrup urine disease because we didn't know if it would cure them,” said Thomas Fishbein, executive director of the MedStar Georgetown Transplant Institute. “It was another leap when we tried putting those livers from children into adults without the disease.”

Only two transplant centers in the country are regularly performing domino transplants that involve children as donors.

Fishbein did his first child-to-adult domino surgery in December, and the University of Pittsburgh Medical Center has done nine of these transplants in the past few years. More centers may try them after seeing the positive results, says Gerard Berry, director of the metabolism program at Boston Children's Hospital, who treats nearly all of the children with maple syrup urine disease in New England.

Adults who have received livers from children have done well with their new organs, with no signs of the diseases that afflicted the children.

“Thus far we have had no metabolic concerns in the recipients, and our patient survival over the long term is thankfully 100 percent,” said George Mazariegos, chief of pediatric transplantation at the Children's Hospital of Pittsburgh, an affiliate of the University of Pittsburgh Medical Center.

One big advantage for patients getting a liver from a child with maple syrup urine disease: Adults with cirrhosis or other liver-destroying diseases, with certain health factors that place them lower on transplant lists, can get a new liver months or even years earlier than they normally would have. Traditional transplants, from deceased donors who had healthy livers, tend to go to the sickest adults who are higher on the transplant lists.

About 17,000 American adults and children are waiting for a liver transplant, and more than 1,500 of them die each year without having the surgery, according to the American Liver Foundation.

“This is a totally new source of livers for such patients,” some of whom may have died waiting to move to the top of the transplant list, Fishbein said.

On Jan. 23, he and five other surgeons and a team of nearly 100 medical staff at MedStar Georgetown performed four liver transplants: two on children with maple syrup urine disease who got livers from people who had died suddenly, and two on adults, including Dick.

Fishbein, who spent 24 hours in the operating room for the complex operations, has perfected the delicate art of removing an entire liver from a person while preserving crucial blood vessels and tissues that will make it possible for the donor to receive a substitute liver. “It's far more complicated” than other transplant procedures, which involve taking a single lobe of the liver from a living donor or both lobes from a cadaver, he said.

The high success rate at Pittsburgh and MedStar Georgetown has generated excitement among specialists, who see it as a win-win for pediatric patients and donor recipients. “We don't have a lot of data on these kinds of domino transplants yet, but I think surgeons can justify doing them,” Berry said.

Since January, Fishbein has performed two more domino liver transplants, involving a child with maple syrup urine disease and a child with amyloidosis. This rare condition — in which plaque builds up in the liver, eventually causing the organ to fail — can shorten a person's life span, but for an older adult with a life expectancy of, say, a couple decades, the new liver will probably last long enough.

“Right now, we can only use livers in those with maple syrup urine disease and amyloidosis,” Fishbein said. “But I believe there will be other conditions that we will identify as being able to reutilize those livers as well.”

Dick says the decision to have the cutting-edge surgery was a “no-brainer” because the autoimmune disease that was destroying his liver had left him exhausted and jaundiced over the past year and was threatening his life.

“I may be one of the first in the world to have this procedure, but the risks didn't seem much greater than if I had a regular transplant,” Dick said.

Quadejah Harris, meanwhile, also sees a better life post-transplant. Ever since she was a baby, she couldn't eat any animal protein — no chicken, no cheese, no beef — and she had to have specially formulated low-protein cereals, noodles, cookies and bread. About 10 days after her transplant, she ate a few bites of turkey for the first time, and said she was really eager to try her mother's fried chicken because it “always smelled so good.”

Even when following their diets strictly, most children with maple syrup urine disease have toxic attacks at least once a year, events that sometimes cause irreversible brain damage. Symptoms start with lethargy and a loss of muscle coordination, which can progress quickly to seizures.

“We see children who look perfectly fine one day and then die within 24 hours or sometimes even faster when they have a metabolic attack,” said Marshall Summar, chief of the division of genetics and metabolism at Children's National Medical Center, where about 70 local children with maple syrup urine disease go for regular care. “They're never really safe until they get a liver transplant.”

Bernard Harris was relieved when his daughter decided last summer that she was ready for a liver transplant; she had been hospitalized for attacks a few times during her elementary school years and has very mild learning disabilities, which doctors attributed to the effects of the disease.

“As much as I worried about the risks of the surgery, I knew it would ensure her level of brain function would not deteriorate more,” her father said.

Such fears also drove Andrea Scott, of Temple Hills, Md., to put her 6-year-old son Korey on the transplant list. Born with maple syrup urine disease, Korey had his surgery on the same day as Quadejah.

Isobel Short, 55, who received Korey's liver, faced the prospect of never getting off the liver transplant list after years of excessive alcohol consumption led to severe cirrhosis. Although the Virginia Beach mother of six said she had stopped drinking 17 months earlier, her liver function didn't improve. Short couldn't walk more than a few steps at a time and was hospitalized to drain excess fluid in her chest, a debilitating effect of advanced liver failure.

“I want to give the young person who gave me this liver the biggest hug and let them know how grateful I am to have a new lease on life,” Short said from her hospital bed before meeting Korey and his mother when they all were at MedStar Georgetown for checkups a few weeks after the surgery.

Korey, who recently enjoyed his first plate of scrambled eggs, was happy to give Short a hug and kiss after she gave him a teddy bear.

“I explained to Korey that when the doctor fixed his tummy and gave him a new liver, he was able to help someone else with his,” Scott said. “I was in awe when his doctors told me his old liver can work perfectly in someone who doesn't have the disease.”