Muscular Dystrophy Association Panel Calls for Expanded Newborn Screening

Rodney Howell, MD, chairman of the Board for the Muscular Dystrophy Association and professor of Pediatrics and chair emeritus of the Department of Pediatrics at the Miller School of Medicine at the University of Miami

Rodney Howell, MD

Newborn screening needs to be expanded to increase the number of infants who have specific congenital disorders, such as Pompe disease, spinal muscular atrophy (SMA), and Duchenne muscular dystrophy (DMD), that can be identified and treated with life-saving interventions.

New guidance from a panel from the Muscular Dystrophy Association (MDA) explored the challenges of universally implementing newborn screening and how the physician community can prepare for this expansion. The group highlighted the opportunities to prevent chronic disability, as well as to optimize newly available life-saving therapies via early diagnosis and the initiation of treatment before symptoms appear in these patient groups.¹

"Newborn screening is one of the most important and impactful public health programs in the United States," said author Rodney Howell, MD, chairman of the Board for the Muscular Dystrophy Association and professor of Pediatrics and chair emeritus of the Department of Pediatrics at the Miller School of Medicine at the University of Miami, said in a statement.² "Since its inception, this program has saved and improved the lives of thousands of children. Its continued expansion to allow for screening for more neuromuscular conditions like Duchenne will benefit many more families by enabling them to receive the care their children need from day one."

Howell was previously named the President of the International Society for Neonatal Screening (ISNS). His 3-year term began on September 11, 2016, at the ISNS International Symposium. He has been involved in newborn genetic screening policies in the US and was the founding Chair of the Advisory Committee on Heritable Disorders in Newborns and Children, which provides recommendations on newborn screening to the US Secretary of Health and Human Services.³

Currently, the US Department of Health and Human Services-endorsed Recommended Uniform Screening Panel (RUSP) includes 35 core and 26 secondary conditions. This special communication from Howell and colleagues expressed a desire to add DMD, among other neuromuscular disorders, to this panel due to the arrival of a number of new effective treatments. Pompe and SMA, which were also not originally included in the RUSP, were added in 2015 and 2018, respectively. As of December 2018, there are 14 states which screen for Pompe and 5 states which screen for SMA.

The authors identified a number of challenges that DMD newborn screening has faced, mainly due to a lack of evidence regarding the effect of early therapy with steroids on newborn clinical development. “Importantly, because 66% of cases are the result of maternal carriers of dystrophin mutations, early diagnosis of the family proband may facilitate appropriate counseling to help prevent additional boys in the same family from being affected by the disorder,” they wrote.

Howell et al recommended that first-tier screening should check for creatinine kinase levels (muscle isoform), while second-tier screening should check for DMD variants. The development of therapies such as RNA-based therapy, micro-dystrophin gene therapy, reducing muscle inflammation and fibrosis, and augmenting muscle mass would all likely be more effective with early therapy, they noted. Additionally, advancements in mutation-specific, muscle-directed therapies support pilot DMD screening programs to explore the clinical applicability of testing for DMD.

"Once affected babies are identified via state newborn screening programs, MDA Care Centers at more than 150 top medical institutions across the U.S. will play a key role in confirmatory diagnoses, treatment, and long-term follow up and care," said Lynn O'Connor Vos, BSRN, president and CEO of the MDA, in a statement.²

REFERENCES

1. Baker M, Griggs R, Byrne B, et al. Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening: Essential Steps. JAMA Neurol. Published online May 20, 2019. doi:10.1001/jamaneurol.2019.1206.

2. The Expansion of Newborn Screening in Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy may Prevent Disability and Save Lives [press release]. New York, NY: MDA; Published May 20, 2019. prnewswire.com/news-releases/the-expansion-of-newborn-screening-in-pompe-disease-spinal-muscular-atrophy-and-duchenne-muscular-dystrophy-may-prevent-disability-and-save-lives-300853338.html. Accessed May 22, 2019.

3. Dr. R. Rodney Howell Elected President of International Society for Neonatal Screening [press release]. Miami, FL: University of Miami Miller School of Medicine; Published September 7, 2016. med.miami.edu/news/dr.-r.-rodney-howell-elected-president-of-international-society-for-neonata. Accessed May 22, 2019.