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#apaperaday: Newborn Screening for Duchenne Muscular Dystrophy – The Time is Now

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Newborn Screening for Duchenne Muscular Dystrophy – The Time is Now

Today’s pick is the white paper from @worldduchenne on new born screening (NBS) for Duchenne muscular dystrophy. The paper is available online and contains detailed descriptions of the why, how and need for NBS for Duchenne. Here the highlights:

The study that I featured a few weeks ago about families with 2 siblings is flagged here as well: parents outlined that there was increased worry when their second child was diagnosed earlier, but they stress that there was more time to plan and treatment was started earlier.

Another argument from people against NBS for Duchenne have is that there is no treatment approved for patients below 4. However, if patients are not diagnosed before age 4, clinical trials cannot occur in this group and therefore treatments will not be approved…

The only way out of this conundrum is NBS argues. Furthermore, I would like to add that the average age of diagnosis is 4-5, which means that for many patients the optimal time to start steroids is in the past when they are diagnosed…thus reducing benefit.

Duchenne parents are very clear about NBS: they outline that it would allow them to be better parents. From a psychosocial aspect, better parenting will lead to a better operating family unit which is also beneficial for the child with Duchenne.

Health care professionals focus on the opportunity to start care early, and to start counseling and carrier screening and to allow families time to consider trial participation. Authors outline that pilots have shown that NBS is feasible. Usually a two-tiered screening is done.

First blood analysis is done to see whether creatine kinase (marker for muscle damage) is elevated. If so, DNA analysis is done. For now usually first exon deletions and duplications are studied first with MLPA (75%) & then Sanger sequencing is used to find small mutations (25%).

In the future, likely it will be more cost-effective to just do whole exome or whole genome sequencing in one go. Authors stress that NBS is not only a test, but that there is a wider infrastructure around it, that involves governance and education of those involved.

Finally, authors stress equity & raise the point if girls should be screened. Some female dystrophinopathy patients have an early onset & these would be detected. Furthermore, there are of course also considerations for cardiomyopathy risks later in life and reproduction aspects.

However, it should be stressed that some girls who are carriers will not have elevated CK. So it is important to remember that for carriers the NBS screening can be negative for dystrophinopathy. This is part of the education that the authors already mentioned.

The document contains more details (that you can read for yourself) and also has appendices on Duchenne, its care and approved therapies and those in development and an outline of NBS pilots, and the key principles for NBS.