 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 Joanne 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 Ventiti, 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. Stephanie's 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, 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. 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 dialysis, emergency hemodialysis, they have a chance of passing away. Some babies that escaped this neonatal crisis, and again in the U.S. we're screening babies, all babies for MMA. 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. 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. That was a nightmare at first. She had severe, severe, severe complications and was on the ventilator for three weeks. We weren't even sure she was going to wake up. So we were really nervous and scared. And then when she did wake up, she couldn't move. I mean, seriously, she was just laying there and just screaming. And then 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 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 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 has been really good. Yeah. A lot more mobile. She eats. She's energetic. Yeah. This form of MMA is called cobalamine C deficiency or CBLC. These patients can have serious health problems if not diagnosed early and often have vision issues 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. He's three years old. He likes playing a lot. He's very handsome. He's very excited. He likes playing a lot, running. He's a happy boy. I think he is always smiling and playing and he loves us too much. Every time he calls for mommy and daddy and he's a happy boy. He was born in April 10 in 2015 and everything was okay in pregnant. Everything was okay, but when he has 20 days of life, we start to think anything was wrong. And then we go to the hospital in Brazil. Dr. Venditti and Tim, we are so thankful for everything you've done for us. Since the beginning, our Bible is the articles of Dr. Venditti and Tim. We met Dr. Venditti last year on the conference that was in Rio. Dr. Venditti and Jen and Dr. Irene, they saw Shandil and he's very well. He's doing great. You're doing a great job. It was like a bit of a conversation, nothing very specific. And we were trying to get here since the beginning because always we think where we can go with Shandil, a place that can help him to be better and better. Yeah, since the diagnosis, we wanted to be here. But Shandil was very young and maybe he could not do all the exams. So we have to wait a while and we were very, very, very excited to be here and waiting for this moment so long. And now we are here. Yes. And our family from Brazil, and there's been a number of wonderful families from Brazil with cobalamin C deficiency that I've 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 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 methylmalon, coenetase. Some people say mute. I say MUT. That is the more severe type. It was wonderful. It was really comfortable for us to see that people are interesting in CMLC and that people are... They are very kind. They are very... It's like being at home, starting from the children's in. Everybody there and the team here, Dr. Venditti's team, they are very kind. They are very helpful. Well, we are very supported here with the team. We really trust in everything they are doing here. The next stage is 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, no 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. I really hope to see that future families, kids don't have to go through all of the illnesses and mist out on things and sicknesses. And then they can have a quality of life that's similar to what a child's life is 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 enjoy things that they like to do, then it would... Of course, I wish she didn't have to go through all the bad stuff and lose things. But it'll be nice to know that she helped others. No, we feel deeply connected, not just myself, but all the members of my team, two of the families. Because so for 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 a hat or hat, a night of sleep and 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 caretakers and the families. And we feel for the patients every time they get admitted and every time they have a serious medical complication. It's really hard because you've got to be so extra protective and germs and not let people be sick. You can plan things, but you have to know that your plans are going to be canceled if she gets sick. You lose a lot of money if you try to plan a trip because you want to give her 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 then know you have to miss work because now you have to care for her or just even missing 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 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. Well, 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 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.