Newborn Screening for Rare Diseases: Early Diagnosis, Treatment Essential

Marshall L. Summar, MD; Jana Monaco


February 27, 2017

Editorial Collaboration

Medscape &

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Marshall L. Summar, MD: I'm Dr Marshall Summar, here at the National Organization for Rare Disorders (NORD) Rare Disease Summit in Washington, DC. I'm chief of the Division of Genetics and Metabolism at Children's National Medical Center, and I'm absolutely delighted to be talking with Jana Monaco, one of my all-time favorite patient advocates and a parent of children with rare diseases who have benefited from newborn screening. That is going to be our topic today. Jana, thank you so much for coming.

Jana Monaco: Thank you for having me.

Dr Summar: Newborn screening is now coming up on its 55th anniversary here in the United States. Of course, we started with a very simple disease: phenylketonuria (PKU), which I hope most of our physicians have heard of. If not, we can review it later.

Where you come into the picture is when we started expanding newborn screening around tandem mass spectroscopy and started to pick up such diseases as organic acid disorders. I'm going to let you pick up the thread a little bit and tell me how a newborn screening affected your life.

Ms Monaco: As you said, we came into this when tests were being developed for other conditions. I entered the rare disease newborn screening world when my son, Steven, was diagnosed with an inborn error of metabolism 15 years ago. Unfortunately, it was not with newborn screening. He went into full-blown metabolic acidosis at age 3 and half and was diagnosed with this condition.

Dr Summar: And then you had your second child, who also has an inborn error of metabolism. Hers was picked up very early on. What kind of difference has that made for Caroline?

Ms Monaco: Unlike her brother, who suffered a severe brain injury and is now left with severe disabilities and complex medical issues, Caroline's [disorder] was picked up before she was even born and was confirmed with newborn screening. The difference is that she just turned 14 years old and is living a normal, typical life that most of her peers do, despite her disorder.

Dr Summar: I'll occasionally see a physician working up a patient whom they think might have an inborn error of metabolism. When we talk about inborn errors of metabolism, we're really talking about disorders in the basic cellular biochemistry. These are usually inherited conditions, autosomal recessive.

You've actually sat on the Secretary's Advisory Committee for newborn screening. You just got back from the mid-Atlantic conference on newborn screening programs. Where do you see this all heading with newborn screening? What is the future looking like?

Ms Monaco: Thankfully, the future is that all babies are pretty much getting screened. All the states have expanded, so newborn screening looks very different than it did 15 or 20 years ago. Where it's headed is for every medical professional who is going to encounter a baby or child to be up to speed, educated, and aware of what newborn screening is, what it means, and the impact that it has.

Dr Summar: Some of the conditions that we screened for very early on, such as PKU, we had very clear treatments for. The one for your family, obviously, we had a good treatment for. Caroline is doing very well. There's a trend now of starting to screen for diseases that we may not have a strong treatment for, or that may have less predictable patient responses to treatment, or that have no treatment at all. What do you think the trends are?

Ms Monaco: I understand from an education perspective that a lot of focus has to be on understanding these treatments and improving them. However, I also see from our own condition that the treatment has changed. It's changing. It's evolving as people are learning more about it and how to handle it. I don't think that the conditions that are coming through the pipeline to be screened for are going to be able to hold to those criteria because of the uncertainty of it. It doesn't mean that we should overlook them.

Dr Summar: One thing that most of our listeners may not know is that newborn screening legislation is passed on a state-by-state basis and, in some states, on a condition-by-condition basis. We can often get pressure from different areas, such as parent groups, physician groups, and occasionally even from industry. Where do you see the roles? Who should drive that bus as we're going forward?

Ms Monaco: The states are looking to see what's coming from Washington, but just like for all the other conditions over the years, patient advocacy groups are really knocking on the door and saying, "Don't forget about us. We have these conditions. What do we do?" I don't think we can ethically leave these families and these patients by the wayside and say, "We don't have the perfect treatment for them, so come back to us later." We owe these families and patients the time and the effort and attention to really address it and find something in the interim for how to handle these situations. They exist, and they're not going to go away.

Dr Summar: There have been some new trends in newborn screening around congenital heart disease using a pulse oximeter. Do you see anything else coming along like that? You've stayed pretty involved in what's new. Is there anything that would not be off of the classic heel stick?

Ms Monaco: That's probably the most different one. Cystic fibrosis has been different from the heel stick, the way it's being screened for, but I think it's going to change. As I mentioned earlier, it will not be so simple and cut and dried, like our organic acidemias were when we expanded 10 years ago. It's going to be different, and I think science has to keep up with it.

Dr Summar: Our job is to try to catch up with all of these things. The one that I see coming along that I think is going to prove challenging in a couple of different ways is the use of DNA. As you know, several states are now screening for severe combined immunodeficiency (SCID) using DNA testing. There have been a number of proposals out there to substitute DNA for the classic biochemical markers, at least for some of these conditions. Do you see any upsides or downsides to DNA being used by state laboratories?

Ms Monaco: As far as the DNA goes, they're going to go through the scrutiny that the blood spots did years ago when states weren't screening for certain conditions but screening for others. You have all the information in those blood spots, but you overlooked them or didn't turn on the markers for those. It's going to be challenging, but I don't think it's necessarily one to avoid, because there are so many possibilities if handled the right way, with a lot of transparency.

Dr Summar: One of the biggest issues in newborn screening is what we call the false-positive or false-negative. You want to avoid those as much as you can. As DNA is brought forward, we don't know the meaning of all the changes we find any more, so I think there will be many false-positives. As a parent, how do you feel about the state laboratory having your child's DNA? Do you see any privacy issues around that?

Ms Monaco: As long as there is transparency and parents are educated and communicated with to understand the purpose, I'm fully supportive of it. I'm the parent who had the child missed because of the state we live in, so I know the significance of a true-positive that went missed vs a false-positive. If having the DNA for my children can avoid that, then I fully support it, but it has to be done properly.

Dr Summar: Another issue that comes up from time to time is that states will have programs that finance the actual newborn screening itself, but don't have a way to finance the treatment, including medications, medical foods, special formulas, and physician care. Is there a message you want to get out there to our physicians about the importance of following through after the original newborn screen?

Ms Monaco: Following through for every baby is critical. Some states have their programs, and some don't. I firmly believe that every state can step up to the plate and find the funds to support these programs. If you're going to screen them, then you need to treat them, and it has to be accessible to patients. I do believe that they can find funding.

Dr Summar: Another thing that comes up from time to time is the idea of a center of excellence. There are two models for how we treat these patients. One is to try to educate as many people as we can in the community, so that lots of folks may be able to help take care of these patients. The other is to develop centers that work with the local physicians and have deep expertise in this. I have a bias for one model over the other, obviously. I run a large genetics program. What does your experience tell you?

Ms Monaco: Because of our personal experience, I can't emphasize enough how important the service center of excellence is. I believe we wouldn't be here today, in a sense, had my son been at a center for excellence. However, it's important that all centers are truly educated. These are no longer those few small rare diseases that no one has to address, because with newborn screening, these babies are thriving, they're living, and they're growing up. Physicians are going to encounter them, so everybody has to jump on board and be a part of the team.

Dr Summar: A big question that comes up now is about transitioning to adolescence and adulthood. It's something that you have to think about a lot. What advice do you have for folks who have younger children or for physicians who are taking care of younger children? What do they need to plan, and what do they need to be thinking about as their kids get older?

Ms Monaco: The physicians who are taking care of the children have to understand that they cannot just identify that child just for their condition, but recognize that it's a part of them. They can manage the whole child for regular primary care issues. There has to be a big collaboration with the specialists in order to manage that care and transition. My transition for these children does not look the same as it does for other children, and I know that that is a big challenge. The fact is that there are so few specialists like yourself.

Dr Summar: A good point that you made before was that the relationship between the primary care provider and the specialty center is absolutely key. They do need primary care providers, particularly folks who are taking care of the rest of the family.

Another thing I would point out is that for a general practitioner, these are some of the most interesting patients they will ever work with and some of the best families. We've certainly enjoyed working with your family over the years. There is a lot to learn that adds to the rest of their practice, too. It makes them better doctors, working with such patients as Steven.

Ms Monaco: You have those that are complex, like he is compared with his sister—although she has her own complexities and challenges. In a perfect world, I would love to see a freestanding specialty care center that has a primary care physician as part of the team, and that's where you could take these patients.

Dr Summar: The whole concept of a complex care system for these patients.

Ms Monaco: Exactly.

Dr Summar: We'll start recruiting generalists now. Maybe this video will help some.

Any messages you'd like to send out there to the general medical community about newborn screening, the importance of it, or things that you'd like to see it do?

Ms Monaco: As much work as we have done to expand newborn screening and to educate and raise awareness in the general public and the medical profession, the medical profession has to embrace it and not underestimate it—to value that newborn screening result as much as they do any other information that comes from that newborn, and to look for those results and make sure that they are informing the parents of what their newborn screening result is. Don't leave anything untouched. Dot the Is and cross the Ts, so that people can walk away and say, "This was my newborn screening result." Families know the Apgar scores for their babies, and they should know their newborn screening results.

Dr Summar: I can't think of a better note to end on. That was greatly said.

This is Marshall Summar from Children's National Medical Center, here for Medscape at the NORD Rare Disease Summit, speaking with Jana Monaco. Jana, thank you so much.

Ms Monaco: Thank you.