Screening Newborns' DNA -- Why Not?

Impact and Evolution of Rare Disease Screening and Treatment

Marshall L. Summar, MD; Jess Gilbert Thoene, MD


February 05, 2015

Editorial Collaboration

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Marshall L. Summar, MD: I am Marshall Summar, chief of genetics and metabolism at Children's National Medical Center in Washington, DC, for Medscape Rare Diseases. I am at the National Organization for Rare Disorders (NORD) Rare Diseases and Orphan Products Breakthrough Summit, speaking with Dr Jess Thoene, one of the founders and pioneers in the field of inborn errors in metabolism in rare diseases. Dr Thoene is professor of pediatrics at the University of Michigan. We are going to talk about some trends in newborn screening and the impact of the Orphan Drug Act.

Let's talk first about newborn screening. It has gone through huge changes and a big evolution over the years from our original phenylketonuria (PKU) test now to the expanded newborn screen. What do you see as some of the directions and some of the benefits? Where is it heading?

Jess Gilbert Thoene, MD: That is a great question and one that allows us to discuss whether a new platform is going to be introduced for newborn screening technology. Previously, it was done by metabolite (initially for PKU) by heelstick blood, and now the possibility for DNA testing with a totally different platform exists. It may allow us to detect hundreds of diseases, ideally diseases that present in the newborn period, need early treatment, and have treatment available.

Dr Summar: I am asked by a lot of pediatricians why we aren't just doing DNA testing for everything already. What do you see as some of the challenges in using DNA testing for newborn screening?

Dr Thoene: There are a number of challenges, and some of them have been outlined by the American College of Medical Genetics. When you look at whole genome sequencing or whole exome sequencing, you find things that you didn't intend to find, and this induces risk and anxiety in the patients. This poses a whole new ethical dilemma about who to tell what was found when you are looking for only specific diseases.

There are solutions to that. You can agree to not disclose what you find other than the newborn conditions that you are screening DNA for; however, that leaves one liable to someone saying, "If you knew that I could have cancer when I am 50, why didn't you tell me?" So there are issues and constraints in this as well as potentially great advantages.

Dr Summar: You say it is an emerging technology. Maybe it is not quite ready for prime time just yet?

Dr Thoene: Probably, but it may be ready sooner than either of us would believe.

Dr Summar: Yes, there are a lot of ethical choices and ethical dilemmas. Obviously, it creates a situation where we may have information about a patient that we don't necessarily share with the patient or we don't know ourselves by masking.

Do you see that evolving over the next 5-10 years? What do you think the realistic timeline is for bringing DNA into newborn screening?

Dr Thoene: A timeline of 5-10 years is technologically feasible. Whether the ethics and the payers and all the rest of the issues that go along with it are ready is a different question, but I would guess that we may be able to implement the technology within 5-10 years.

Dr Summar: It sounds as though we will need a bigger workforce in genetic counseling to help the families understand the testing.

Dr Thoene: Absolutely. Today, every time we send a whole exome screen out and get the results, it takes 4 or 5 hours of genetic counselor time and an hour of clinician time just to be sure that we are presenting the results accurately and intelligibly to the patient. If that is multiplied by all the newborns who would be screened in the United States, it is a huge increase in workload.

Dr Summar: This is not something that we are just going to report out on a form and give to somebody.

Dr Thoene: Ideally not.

Dr Summar: Dr Thoene, you have also been involved in some of the early days with the Orphan Drug Act and were among those who were instrumental in its passage here in Washington, DC.

We just had the 35th anniversary of the Orphan Drug Act. What has made the biggest impact? What do you see for the future?

Dr Thoene: The Orphan Drug Act in 1983 was enacted in response to the fact that there were very few treatments for what we now know to be rare diseases. These were defined in the Act as conditions that affect fewer than 200,000 Americans. There were 10 extant orphan products at the time that the Orphan Drug Act was enacted. Now, there are 300. The world market is $62 billion. It exceeds what anyone imagined back in 1983 that it could become such a huge commercial success and bring treatment to so many patients with diseases that had absolutely no treatment.

I can't imagine how quickly it can continue to grow, but there are 7000 rare diseases, so we have 6700 still to work on.

Dr Summar: As we watch the evolution of genetics into personalized medicine, do you feel that the Orphan Drug Act provides a model as we individualize care and treatment for the common, regular patient?

Dr Thoene: It could. That raises the question of whether enhanced genetic screening—molecular DNA analysis—will be parlayed appropriately by diagnostic laboratories, and whether payers will pay for it, allowing us to further refine diagnoses so that we know which treatment is best for which specific subtype of disease. It is an open question, but it opens up that opportunity.

Dr Summar: I can't thank you enough for coming in and talking with us today. Your insights on rare disease in newborn screening are going to be very valuable to our readers. It is an exciting time in genetics and rare diseases as the two fields grow closer. The future is going to be exciting, and we look forward to new developments and seeing how some of your predictions turn out.


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