Steve Wewerka for The New York Times
Hannah and Scott Stimell. Her hair growth is a drug side effect.
Posted on 12/27/2004 8:04:01 PM PST by neverdem
MINNEAPOLIS - Dr. Mindy Rauch thought she was humoring her brother at a family gathering last Father's Day when she agreed to examine his 6-month-old daughter, Hannah. The baby's stomach worried him: it felt taut, and too big. Dr. Rauch, a pediatrician, thought her brother was just another nervous first-time father.
"Oh, look at this belly," she said playfully, feeling the baby's middle. A moment later she turned to her husband, who is also a pediatrician, and said, "You have to feel this."
Hannah's liver and spleen were enormously enlarged. It was a sign of serious illness: possibly a tumor, a viral infection or a genetic disorder.
For Hannah's parents, Scott and Jill Stimell, the next few weeks became a series of desperate trips to doctors and hospitals.
On July 16, the answer came: Hannah had a rare genetic disorder, Niemann-Pick disease type A.
It is hard to imagine a worse diagnosis. Infants with the disorder seem normal for the first few months, but the disease is already damaging the brain, the liver, the lungs and other organs. There is no treatment. The babies weaken, fade mentally and die, usually before they turn 3.
Within hours of learning Hannah's diagnosis, the Stimells faced an agonizing choice: they could watch her die, or pursue a drastic and painful treatment that had never been used successfully on a child with her condition. The treatment, chemotherapy and a transplant of umbilical cord blood, might save Hannah, do nothing or kill her. It also might save her body, but not her mind.
"Possibly we could save my daughter's life, but then she could be a complete vegetable for the rest of her life," Mr. Stimell said. "Do I put my little baby through this hell knowing there's a great chance it won't work?"
And yet they felt it would be unbearable to stand by and do nothing.
"We felt like we had to take a shot," Mrs. Stimell said. "She's a fighter. She has something in her."
Niemann-Pick is one of about 50 metabolic disorders known as storage diseases, in which a substance the body should break down instead builds up and causes illness. In this case, a fatty molecule, sphingomyelin, accumulates because patients lack an enzyme needed to degrade it. There are several forms of the disease; type A is the most severe.
Why excess sphingomyelin causes so much damage is not clear, said Dr. Edward Schuchman, a professor of human genetics at the Mount Sinai School of Medicine in Manhattan. The molecule is a normal component of cell membranes, but too much of it may alter the membranes and disrupt cell function, Dr. Schuchman said.
The enzyme to break it down is missing because of a genetic mutation. For a child to be affected, both parents must carry the defective gene. Then there is a one in four chance of having an affected child with each pregnancy. But carriers have no symptoms.
Niemann-Pick, Tay-Sachs disease and several other genetic disorders are more common in Jewish people with ancestors from Germany, Poland, Austria or Eastern Europe - Ashkenazi Jews - than in other groups, and many Jewish couples seek genetic tests before having children. If both parents are carriers, the fetus can be tested, and if a devastating disease is found, some couples end the pregnancy.
The Stimells were stunned by Hannah's diagnosis because Mrs. Stimell had been tested for Niemann-Pick and told she was not a carrier. Later, a test showed that she carried a rare mutation not picked up by the standard test.
The day Niemann-Pick was diagnosed in Hannah, an uncle who is a pediatrician began searching the Internet and found that doctors at Fairview-University Children's Hospital, at the University of Minnesota, were treating storage diseases with transplants of bone marrow or umbilical cord blood. The family contacted Dr. Charlie Peters, who told them that the group had not been treating Niemann-Pick type A. In the past, they had tried bone marrow transplants in two babies with the disease, but the treatment failed and both died.
However, Dr. Peters said, the technology had advanced, and a transplant might now be worth considering. But the family would need to act fast, he warned, because the disease progresses rapidly.
A week later, on July 24, the Stimells, who live in Long Beach, N.Y., flew to Minneapolis.
Doctors began using bone marrow transplants to treat storage diseases in the 1980's. Performed early enough, the transplants can save children's lives and halt progressive brain damage. The University of Minnesota, which has treated several hundred children, is a leader in the field, along with Duke University, which has treated about 100, including some newborns.
Bone marrow contains stem cells that produce blood and immune-system cells. Blood from the umbilical cord and placenta, collected after a baby is born, is also rich in those stem cells, and in the 1990's doctors began using it for transplants.
Hundreds of thousands of cord blood samples have been frozen and banked, and are available immediately if a donor and recipient have matching tissue types. Bone marrow takes longer to acquire because it is not usually banked but is collected from donors only when it is requested for a matching recipient. Because Hannah has a progressive disease, her doctors hoped to use cord blood rather than a bone marrow donor so they could start treating her as quickly as possible.
To perform a transplant, doctors wipe out the patient's bone marrow with chemotherapy and then replace it with marrow or cord blood, which creates a new blood supply and immune system. The new cells can also provide the missing enzyme for someone with a storage disease.
The cells include white blood cells called monocytes, which can become part of the liver, the lungs and the brain. If a transplant can help a baby like Hannah, it will be these cells that save her, researchers say. Her brain, as well as other organs, needs the missing enzyme to break down sphingomyelin, but the enzyme itself probably cannot pass into the brain, researchers say. Monocytes, however, should be able to reach the brain, take up residence there and make the enzyme.
In Minneapolis, doctors evaluated Hannah to find out whether she was strong enough to withstand the chemotherapy and the transplant, and whether her brain was intact enough to make it worthwhile.
"The decision to transplant is very complicated," said Dr. Lawrence Charnas, a neurologist. "You want to do the right thing, but you don't want to keep an individual alive when they can't interact and have no chance of development. We don't want to prolong dying."
Dr. Peters said he often had to tell parents it was too late to treat their children, and he initially suspected that would be the case with Hannah.
But Dr. Charnas pulled the Stimells from the brink of despair.
"He said, 'There's a light behind her eyes,' " Mrs. Stimell recalled. A neuropsychologist, Dr. Elsa Shapiro, agreed, declaring that although Hannah had developmental delays in some areas, in others she was not too far behind.
"She looks at you very intently," Dr. Shapiro said. "She always looks people straight in the eye."
"You really get a sense that there's somebody there," she said.
They would be in uncharted waters with a transplant, the doctors said, but it was not unreasonable to try.
Mrs. Stimell said, "It gave us a glimmer of hope, and we decided to go with that."
There was no time to lose. In babies with storage diseases, toxins build up constantly. In some diseases, just a week can determine if a child will ever walk, experts say.
"Time is brain," Dr. Peters said.
Hannah struggled through eight days of chemotherapy, which caused such severe mouth sores that she stopped eating and was given morphine for pain. On Aug. 21, she received a cord-blood transplant: an infusion of cells, much like a transfusion, that took only about a half-hour.
In the weeks that followed, she had severe breathing problems, her hair fell out and she had to wear a surgical mask because antirejection drugs left her vulnerable to infection. She became sick and ran a fever. But the transplant took, and within a month her enzyme levels had gone from zero into the normal range. Sixty days later, the levels were even higher. Her liver, though still enlarged, shrank considerably, as did her spleen.
"We're all tremendously pleased at how well this little girl is doing," Dr. Peters said. But, he cautioned, "It's still sort of preliminary."
[On Dec. 15, after nearly five months in Minneapolis, Hannah returned home to Long Beach with her parents.]
It is too soon to tell whether the transplant will save Hannah or protect her brain. The doctors do not yet know whether the enzyme is reaching her brain, or whether it will prevent further damage if it does get there. Brain scans and other tests scheduled for February may provide clues. But time will be the real test.
Doctors are also unsure how much brain damage Hannah has already suffered, or whether she will be able to overcome it. Her development is still "delayed," her doctors say. At 11 months, she is at about the level most babies reach at 7 months, Dr. Shapiro said. Hannah does not sit up on her own, but if her parents sit her up she can stay that way, though she sometimes wobbles and falls over. Unlike most children her age, she is not crawling, babbling or trying to pull herself up to stand. Her legs are thin and weak. She does not eat enough and must be fed through a tube that runs through her nose into her stomach. She needs intensive speech and physical therapy.
But the doctors say they are encouraged because she has made progress at a time when, given the usual course of the disease, she would be expected to regress.
"We're now four months from transplant," Dr. Shapiro said. "She is stable, has not lost any milestones or functioning."
Dr. Charnas said, "I don't know whether she will ever catch up, but the fact that she's moving forward is generally a good thing."
The team was encouraged to hear recently that a baby with Niemann-Pick type A who was given a cord-blood transplant at the Hospital for Sick Children in Toronto at 3 months was also doing well six months later.
Hannah Mollie Stimell's eyes are big, dark and shining. Before the transplant, she was beautiful. Now she is also impish, with a startling new crop of dark hair on her chin and forehead, including what Mr. Stimell calls "Bert and Ernie eyebrows," temporary side effects of the antirejection drug cyclosporine.
Hannah has her father figured out, and, he freely admits, has him trained to respond to her every peep by scooping her up, parading her around and singing to her.
"I believe in my heart of hearts there will be some sort of miracle," he said. "I don't know if she will walk or talk, but I believe she will."
Steve Wewerka for The New York Times
Hannah and Scott Stimell. Her hair growth is a drug side effect.
God bless and help this baby and her family.
stem cell ping
Thanks for posting. My brother died of Niemann Pick type A at the age of 10 in 1963. Terrible disease. My prayers go to this little girl and her family.
FReepmail me if you want on or off my health and science ping list.
Amazing story--thanks for sharing!
Great testimony to the fact that stem cells can be obtained without killing an unborn baby.
The daughter of a good friend recently had a stem-cell transplant--USING HER OWN STEM CELLS in a procedure similar to this one, for Crohn's disease. She's doing well.
I don't advocate allocating big bucks to research rare and obscure diseases such as this, even having been touched by one but it's good to see another possible, amazing use for umbilical stem cells, rather than fetal.
My prayers and heart go out to Hannah and her family.
After going through the chemo and everything else, it's a miracle she didn't regress! These "milestones" aren't fixed in stone anyway, so the little girl's future may be very bright.
My daughter didn't follow these milestone rules. Nothing wrong with her, but the doctors were very concerned about her development. Didn't roll over much and was "late" with that skill. She never crawled, but rather just slid on her rear-end everywhere. That was after I would put her in a sitting position. Then she caught on and would sit up herself. And she didn't care to stand either. At some point I propped her up at the coffee table, stood a couple of feet away, smiled and waved. She figured this out soon enough and was walking within a week. Up until then she wouldn't even put weight on her legs.
There's obviously a lot of variation in the way children develop.
Hannah's trait of intently looking people in the eye speaks volumes. She's going to surprise a lot of people. You can see it in her eyes. She just might be one of those diaper-scooters. :-)
What an amazing story. God Bless this precious little baby and her parents. I pray that this treatment gives her the chance to live a normal life.
Thank God she wasn't born in the Neterlands. The doctors would have introduced the gun with a single bullet in the chamber already.
At least she will know joy until the age of ten or so. God bless her and her family.
Apf
Absolutely!
I am so proud of my daughter who works at a place that freezes and stores cord blood. Praise the Lord for research that developes these medical miracles.
Please let me know if you want on or off my Pro-Life Ping List.
Although it a major sin for old main stream media not to delve on any thing other than how wonderful it is to have sacrifrificial children as a source of immortality, it's nice to see that stem cell research is more vast than what they would you to believe.
People harvesting babies for body parts! I can't believe in a way we have tolerated selfish sick behavior enough to let this stuff arise.
The 60's are over. Time to start making some judgment calls.
from exp with friends and family with foster children or adopted children that were a little "slow"....these kids can catch up quite quickly given the right circumstances.....
So sad about your brother, fullchroma. I'm so sorry that you lost him to this terrible disease.
What unimaginable trauma this precious baby girl is going through. My heart and prayers go out to Hannah and her family.
Wow!
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