Q&A: What is the 'bubble boy' disease?
Experts explain severe combined immunodeficiency
ST. PETERSBURG, Fla. – It’s almost impossible to start a conversation about severe combined immunodeficiency, or SCID, without referencing the 1976 ABC made-for-television movie “The Boy in the Plastic Bubble” starring John Travolta.
That film, as well as the 2001 comedic-interpretation “Bubble Boy” starring Jake Gyllenhaal, was inspired by the real life of David Vetter, a child born in 1971 with SCID and treated in hospitals inside a specially designed sterile plastic bubble. Vetter died in 1984 at the age of 12.
During News 6's story with Central Florida resident Heather Smith, we spoke to two doctors in St. Petersburg, Dr. Jennifer Leiding and Dr. Jolan Walter. Both women are immunologists, allergy specialists and associate professors of pediatrics at the Morsani College of Medicine at the University of South Florida.
Leiding is the medical director of the SCID Newborn Screening Program at Johns Hopkins All Children’s Hospital; Walter is the Robert A. Good Endowed Chair in the USF Division of Pediatric Allergy & Immunology.
They both know a lot about infant immune systems and specifically a lot about SCID.
We had a handful of soundbites from both Leiding and Walter. And though the information we used was important and relatable to the story, each woman had a lot more to say about SCID that we didn’t include.
As we do on occasion, we like to reprint portions of interviews with newsmakers to give our audience a better understanding of a topic.
Below you’ll find an edited version of topics we covered with both Leiding and Walter.
Dr. Jennifer Leiding interview:
WKMG: A lot of people don’t think they know about SCID -- severe combined immunodeficiency -- but they do because they’re familiar with the story, the movies, about the boy in a bubble.
Leiding: The boy in the bubble depicted a boy with SCID who at the time when this disease was very new, his doctors didn’t know an optimal treatment. They did know that he needed a bone marrow transplantation but he didn’t have any suitable donors. And so the only way to treat him that was left was to isolate him. His doctors picked the most extreme form of isolation, which was to live in a plastic bubble.
WKMG: But we don’t really do that anymore, do we?
Leiding: There is no need any more for bubbles, but there is still a place for isolation until treatment has been successful. Nowadays, when we diagnose SCID, those patients still are in isolation. They are either isolated at home with very few visitors or caretakers or they’re isolated in a hospital room to prevent infection. A child just being in a normal environment with the things that you and I breathe in every day could cause a deadly infection in a child with SCID, so they still are isolated.
WKMG: Diagnosing SCID has come a long way and can now be done before an infant even shows any signs of the disease. Can you give us some more information on what is known as infant newborn screening?
Leiding: In Florida, every newborn is screened within the first 48 hours of life while they're typically in a hospital. But parents can opt out of the newborn screen should they choose to do so. In that case, their child would not undergo newborn screening for SCID or for any other disease that is present on the newborn screen.
WKMG: As a doctor, do you recommend opting out?
WKMG: Absolutely not?
Leiding: Absolutely not. Every disease that is present on the newborn screen, including SCID, are life-threatening diseases in infancy. The rationale that they’re included on the newborn screen is so that they can be identified early before there’s any associated morbidity or even death.
WKMG: Newborn screening -- is it a relatively new thing?
Leiding: No. Newborn screening started many years ago with the original tests for P.K.U. [ed: phenylketonuria – a disease that decreases the metabolism of infants]. There are now more than 30 diseases that are screened for in Florida, but every state is different and every state has different tests.
WKMG: It sounds like you’re analyzing the problem before it becomes a problem.
Leiding: In Florida, we adopted SCID into the newborn screening 2012. It is now, as of this year, been implemented in every state in the United States. And since 2012 we have diagnosed many cases of SCID throughout the three centers in the state that are responsible for newborn screening and haven't had any children die of SCID-related problems since the implementation of the newborn screen.
WKMG: That has to make you feel good.
Leiding: It’s pretty amazing.
WKMG: If a child is born at St. Joe’s in Tampa, is the testing done there?
Leiding: The blood collection is performed at the hospital that the child was born at and is sent to the state lab in Jacksonville. It is run typically within 24 to 48 hours of receipt and if the newborn screen is abnormal for SCID and the child is from Tampa, our center is notified immediately. We then call the family and have them come in and they are evaluated usually in the first 48 hours of knowing that information. So typically the age of the child by the time that we have had the testing done and brought them in is the first week of life. So they are immediately diagnosed and immediate intervention (is deployed) to help treat their disease should it actually be SCID.
WKMG: So, the key here is intervention. It is not a cure. This is diagnosis and then figuring out how to make life not-quite-perfect but pretty good?
Leiding: We know in SCID if diagnosis is delayed there is a significantly higher risk of infections that can be deadly. And so if the child is even surviving the infection that they develop because of the delay in diagnosis, their likelihood of surviving any therapeutic intervention including bone marrow transplantation or gene-therapy significantly reduces. The concept is that we want to identify these children earlier before those problems occur so that our intervention is more successful.
WKMG: You mentioned bone-marrow transplants and gene-therapy, is that how doctors treat SCID?
Leiding: The only treatments for SCID are to replace or to change or alter the immune system. The standard way to do that as of today is with bone marrow transplantation where you are giving the infant with SCID somebody else’s immune system. Gene therapy is the new kid on the block so to speak. Instead of giving a new immune system to the infant, you are fixing their own immune system. You are changing the way their genes appear and recognize different things so that they don’t need to receive somebody else’s immune system. It’s not that gene therapy has replaced bone marrow transplantation; it’s just gene therapy is newer. There are still a lot of unknowns that need to be worked out before it becomes the standard of care.
WKMG: Our story centers on Heather Smith and her son Taylor, who is now 21 years old. Would gene therapy work for Taylor?
Leiding: There is no age restriction with gene therapy. The older a child with SCID gets the more complications they have. And so the majority of children who have undergone gene-therapy have been younger because they are optimal candidates for that therapy. That being said, Taylor can undergo gene-therapy. His genetic problem has not changed. To modify the gene or give him a new gene would still treat his disease.
WKMG: And again, this isn’t a cure. It’s almost like keeping something in check.
Leiding: The immune system is sort of like a garden. It grows, but you have to maintain the garden or it gets weeds and it stops growing and doesn’t do so well. For SCID, that includes normal healthy lifestyle recommendations and requires constant monitoring to make sure that that immune system isn’t changing or going away. How to prevent that is still a major area of exploration investigation but it’s certainly feasible that it can happen. The goal for our SCID patients is that they at least come in once a year.
WKMG: How does it make you feel when you know you’re saving a life?
Leiding: I have a lot of empathy for families that go through this. I’m also a mother with young children. And I think that’s got to be the worst call of any mother’s life when they’re receiving a call regarding an abnormal newborn screen. And so it’s a hard road and journey that we go on but at the end of the day our goal is that our children outlive us. And so that's what I really strive for so that we can have productive children who are healthy.
Dr. Jolan Walter Interview:
WKMG: Most people know SCID, severe combined immunodeficiency, as the bubble boy syndrome or the disease of the bubble boy. What exactly is SCID?
Walter: SCID, or severe combined immunodeficiency, is a severe immune disorder that is inherited. Mostly it can come from carrier mothers, or a patient can have a genetic variant that they generate as they are in utero and they are born with it. Their T cells do not function or they are not there, so one part of the immune system, a critical part of the immune system is missing. Immature T cells come through the thymus gland and mature to be able to eliminate viruses. When they are not present in our body, we have a hard time taking care of any kind of infection.
WKMG: So it's really about the T cells. There’s not enough of them or any of them to fight off something as simple as a cold, an infection from a cut, or as severe as the flu or pneumonia.
Walter: Newborns are protected by maternal immunoglobulin, so many of these children look perfectly healthy at the time of birth and they can remain healthy up to four to six months of age. Then the maternal antibodies slowly decline, and with that decline, they start to show some symptoms of abnormal reaction to the infection. Some of them would have oral thrush [Ed: a white rash inside of the mouth caused by a weakened immune system] and start losing weight. Other patients would develop diarrhea that they cannot control and many of the parents tell us that my child was just not looking right.
WKMG: And there are two different things in play here: the mom’s immunoglobulin protected them for a few more months and sometimes pediatricians just don't know what to look for.
Walter: Dr. Robert A. Good, who created our center here, was one of the first people who did bone marrow transplantation with the first kid in the 1960s. But interestingly even within that 50 years of understanding the disease better, people could not catch or find the patient in time.
WKMG: And now with newborn screening, you know very quickly what you couldn’t know before?
Walter: Yes. We are very fortunate that in this country the effort of the public has gotten policymakers and many other people in the media, social sector and scientists to come together. Four million newborns are screened every year now for this disease very early in their life unless the parents opt out.
WKMG: And these tests aren’t very expensive but the costs do add up when you’re talking about screening millions of infants.
Walter: Every state makes its own in-house SCID screening tests so it could vary from state to state to state. And we had to really justify the cost by saying that if we don’t find these patients in time, the cost of taking care of them (after the fact) could be five times as high. Elena Perez and her colleagues showed that a SCID patient funded at birth could be around $300,000, but treatment for this patient diagnosed later could be as high as $1.5 million.
WKMG: And these tests are finding more kids with SCID than ever before?
Walter: Initially the incidence was one in 100,000 because these patients were found incidentally through infections. As the newborn screening started, the incidence is one in 58,000, about every second child was missed. We basically lost every second SCID baby because they couldn't find them in time. And we estimate that in this country, we have around 80 patients born with SCID.
WKMG: And there are also geographical and ethnic factors in play?
Walter: That's correct. In California, the frequency is much higher because of the Hispanic population. So we were expecting similar trends in Florida. There are certain pockets of ethnic groups that have a very high frequency of SCID genes. Navajos - Native Americans - they have a high frequency of the Artemis gene that is a SCID gene. Patients who are coming from the Amish communities have a high frequency of SCID genes. So we have to be very sensitive for the origin of the family and see if they will be carrying a higher frequency of the gene.
WKMG: Is there a “severity” of SCID? Can you have it a little bit?
Walter: Yes, it's an excellent question and I'm glad you asked this because SCID is not black and white. You can have a SCID patient who has no T cells at all. And there are SCID patients who actually have a tiny bit of T cells, but they are not really doing their job. They start to multiply and proliferate and can cause bad dermatitis, colitis and even old man syndrome. SCID is a spectrum and many of these patients who are diagnosed with newborn screening could have any variant of SCID. It is very interesting how this new blood screening that was only designed to find SCID is actually helping our field to broaden the spectrum of covering patients very early in life defined by variants of the disease.
WKMG: Is there a cure for SCID?
Walter: We know that we cannot cure but treat the disease. Curing would mean that once we take care of the patient with a therapy that the patient never has to come back and see a doctor, and most of our interventions still need a careful monitoring so we don’t let these patients disappear.
WKMG: We know about the boy in the bubble, but we don't do that anymore do we?
Walter: No we don't. At the time the boy was in the bubble, it was very interesting. He was born in 1971, three years after Dr. Robert A. Good had done the first bone marrow transplant for SCID. So everybody expected that this child who was known to have SCID would receive bone marrow transplantation, but unfortunately had no donor. And because he had no donor the family knew that once he gets outside he will get infections and die. They put him into this bubble to protect him. Around in his teenage years he got a bone marrow transplantation that was successful, but he died from later complications.
WKMG: What's it like when somebody does find you and you're able to say ‘This is what is wrong with your child?’”
Walter: It is always an exciting moment. I get excited because of the discovery … I think it's always an exciting moment because we have learned so much and then a patient comes to you and you realize that what you learned is actually meaningful and could change a life. Very satisfying.
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