The National Institutes of Health, also known as NIH, is the primary agency
of the United States government responsible for biomedical and public
health research.
For 14 years, Stephanie Evans and her mother, Joann, have been
traveling to the NIH Clinical Center in Bethesda, Maryland, to participate in
the study of a rare disease with a big name, methylmalonic acidemia, or MMA.
MMA makes it difficult for Stephanie to break down and process protein in her food.
Toxic acids build up in her bloodstream and cause an array of life
threatening health problems. There are many types of MMA, but Stephanie has a
more severe form of the disease requiring strict dietary management and
avoidance of sick contacts. Illness in these patients can cause devastating
strokes and organ damage. Stephanie eventually had a liver and kidney
transplant to replace her damaged organs. The complexities of her disease
make treatment difficult. One in 48,000 newborns will have MMA.
But there’s hope.
Dr. Chuck Venditti, a senior investigator in the National Human
Genome Research Institute, part of NIH, is working with the largest group of
people affected by MMA. He and his dedicated research team are conducting
a study to understand MMA at the molecular level. Soon they will begin
clinical trials to test several new treatments.
Joann Evans: Stephanie is a spunky little young
lady with methylmalonic acidemia. She knows what she wants to do,
and she lets everybody else know, but she gets frustrated with all her
restrictions of what she can eat and can’t eat, or that it’s a med time, and
that her day is controlled by what medication is needed at what time.
She was born “perfect,” and -- but then she quit eating and went into a
coma on her second day of life. So, she was transported from our local hospital
to Indianapolis -- because we lived in southern Indiana at the time -- to the
local hospital, not expected to live, and then that’s when they diagnosed the
methylmalonic acidemia, on day three.
Charles Venditti: With the symptoms of MMA, many babies
will be affected in the first few days of life. And typically, the baby will
be cold, may not be feeding well. Someone may think the baby has a very
serious infection, which can occur in babies. And the patient or the
baby will slip into a coma. And that baby, unless they're rescued with
usually dialyses, emergency hemodialysis, they have a chance of
passing away.
Some babies that escape this neonatal crisis -- and again, in the U.S. we're
screening babies, all babies for MMA.
Charles Venditti: Hello, good to see you again!
thank you for coming back.
Well, many of our patients, of course, come from all around the United
States, and, MMA is a very difficult condition to manage. We oftentimes
collaborate with all the referring physicians from all the centers around
the United States to help the families with very, very difficult decisions.
For example, deciding when someone might need a liver transplant -- this
is a very big procedure for a child -- or a liver/kidney transplant.
Joann Evans: That was a nightmare at first. I mean,
she had severe, severe complications and was on a ventilator for, like, three weeks.
We weren’t even sure she was going to wake up, so we were really nervous and
scared. But -- and then when she did wake up, she couldn’t move. I mean,
like, seriously, she was just laying there and just screaming. And then,
like, one day she could lift her fingers; then she could lift her hand;
then she got it up. Then she could move her hands, but she couldn’t move the
rest of her body. And so, it took a long time -- I mean, maybe two to three
months -- before she could, like, walk. And so, we had to go to rehab for a
while and stay there for a while until she could walk enough that I could take
care of her in a house without all this, you know, like, extra stuff. We had to
go home with some extra supports, and we had to convert a room downstairs into a
bedroom, because she couldn’t do stairs. And it took her a good year to really
recover from the surgery; now we’re almost two and a half years out.
She’s been really good, yeah. A lot more mobile; she eats;
she’s energetic. Yeah.
Another form of MMA is called Cobalamin C Deficiency, or cblC.
These patients can have serious health problems if not diagnosed early, and
often have vision problems and developmental delays. However, patients
with cblC can be treated with vitamin B12 injections which can help improve
the effects of their disease. A Brazilian couple’s lively son began
showing symptoms of cblC, just 20 days after his birthday.
Meet Xandinho .
Alexandre da Cunha Guedes Neto: He’s 3 years old. He likes playing a lot.
He’s very --
Luana de Brito Soares Cunha: Handsome [laughs].
Alexandre da Cunha Guedes Neto: Yes, he is handsome [laughs].
He’s very excited. He likes playing a lot, running.
Luana de Brito Soares Cunha: He’s a happy boy. I think he is always --
Alexandre da Cunha Guedes Neto: Smiling.
Luana de Brito Soares Cunha: --smiling and playing. And he loves us
too much [laughs], and every time he calls for Mommy and Daddy -- and
he’s a happy boy.
He was born on April 10 in 2015, and everything was okay -- in pregnancy,
everything was okay. But when he has 20 days of life, we started to think
anything was wrong, and then we went to the hospital in Brazil.
Dr. Venditti and team, we are so thankful for every thing.
And since the beginning, our bible is the articles of Dr. Venditti and team.
Alexandre da Cunha Guedes Neto: Yeah, we met Dr. Venditti last year at a
conference that was in Rio, and Dr. Venditti and Jen and Dr. Irini --
they saw Xandinho, and -- “Oh, he’s very well. He’s doing
great. You’re doing a great job.” And -- well, it was, like, a bit of a
conversation; nothing very specific.
Luana de Brito Soares Cunha: And we were trying to get here since the
beginning, because, always, we were thinking where we can go with Xandinho,
a place that can help him to be better and better.
Alexandre da Cunha Guedes Neto: Yes, since the diagnosis we wanted to be
here, so -- but Xandinho was very young, and maybe that he could not do all the
exams. So, we had to wait a while, and we were very, very, very excited to be
here and waiting [laughs] for this moment so long, and now we are here.
Charles Venditti: And in our family from Brazil -- and there's
been a number of wonderful families from Brazil with Cobalamin C Deficiency that
have reached out to myself and members of the team -- some of them have what looks like
slowing or delay of their eye changes. that's why we would, consider patients that
are not from the United States as very important to teaching everyone about the
condition, not just children here in the U.S.
Since I've been at NIH and saw -- since we saw our very first patient in
2004, I've had a chance to evaluate many, many patients with MMA,
all different forms of MMA. I think we are over 200 patients that we're following now
with types of MMA, and many of them have the MUT deficiency type.
Now with the MUT deficiency type -- MUT stands for methylmalonyl-CoA mutase.
Some people say mute. I say MUT. That is the more severe type.
Luana de Brito Soares Cunha: It was wonderful. It was really
comfortable for us to see that people are interested in CblC and that people are --
Alexandre da Cunha Guedes Neto: Yeah, they are very kind. They are very
-- it’s like being at home. Starting from the Children’s Inn, everybody there in
the team here -- Dr. Venditti’s team -- they are very kind.
They are very helpful. Well, we are very supported here with the team.
Luana de Brito Soares Cunha: We really trust in everything they are doing here.
Charles Venditti: The next stage is when we were --
what you mentioned, is getting ready for an interventional trial. And this is going to,
we think, soon -- we are hopeful very soon that we will be having new therapies for
MMA, new genomic therapies. And there's three different types that we've been
working on. One is an MRNA or Message RNA-based therapy, the other is an AAV,
Adeno-associated viral gene therapy protocol. And the last one is one that
uses genome editing to try to fix the gene in the liver of the patient.
Joann Evans: I really hope to see that future families --
-- kids don’t have to go through all of the, illnesses and miss out
on things and sicknesses, and then they can have a quality of life that’s, similar to
what a child’s, life is. You know, to be able to do things.
And she lost her hearing and her vision, suspected because of the MMA.
So, if they could have treatments and still be able to see and hear and, you know
enjoy things that they like to do, then it would -- of course, I wish she
didn’t have to go through all the, you know, bad stuff and lose things, but
it’ll be nice to know that she helped others.
Charles Venditti: No, we feel deeply connected,
and not just myself, but all the members of my team to the families,
because -- so if we're taking care of the patients for all the years,
we really know just how difficult it is for the children and for their parents.
Stephanie's mom, I think -- I don't know if she's received -- had a -- had a
night of sleep in her -- in 20 years, 30 years. I think she's basically -- every
waking moment is checking on her daughter all night long; adjusting her
feeds, checking her G-tube, making sure she gets her medicines, making her
formula. It's really an unbelievable effort, so we really feel for the
families. We know how difficult it is for all the care-takers in the families
with MMA. And we -- you know, we feel for the patients every time they get
admitted and every time they have a serious medical complication.
Joann Evans: It’s really hard, because you’ve
got to be so extra-protective, and germs, and not let people be sick.
And you can’t really -- you can plan things, but you have to
know that your plans are going to be canceled if she gets sick, you know.
You lose a lot of money if you try to plan a trip, because you want to give her,
you know, the best of life, but then you’ve bought your tickets, and she’s sick,
and you can’t go. And then trying to work full time, but to
care for her, and then be sick and know you have to miss work, because now you
have to, you know, care for here. Or just even miss seeing with all the
appointments, and so then you’re working very, very long days to make up your hours
because you missed during the day, you know, to take her. But then to also
try to give her -- I hate using the word “normal,” but to try to give her a normal life
and let her do all the things that she should be able to do.
Charles Venditti: I guess the only other thing I would say would be,
you know, we're so appreciative for all the families coming to participate in
our study. And for some families, this can mean taking the entire -- their
entire vacation instead of, as we would think going to the beach or going to a
lake or going on a trip. They come to the NIH, and their child with MMA is
admitted to the hospital and the children donate blood to our study.
The families donate blood and they spend all their time, precious vacation time, away
from work even. Some people have had to take medical leave to come here to be in
the study. And so, we're really appreciative of all the families and all
the children that have given literally their blood and time to us. So, for that, I'm super appreciative.
And just so that the families know, we would be nowhere without them.