Screening of newborns for neurogenetic abnormalities

Aram Kim MD (

Dr. Kim of Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, has no relevant financial relationships to disclose.

)
Deepa S Rajan MD (

Dr. Rajan of Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, has no relevant financial relationships to disclose.

)
Nina Schor MD PhD, editor. (

Dr. Schor of the National Institutes of Health and Deputy Director of the National Institute of Neurological Disorders and Stroke has no relevant financial relationships to disclose.

)
Originally released April 9, 2015; last reviewed November 1, 2020; expires November 1, 2023

Overview

As we move into the era of genetic testing and personalized therapies for rare diseases, understanding the history and evolution of newborn screening for neurologic diseases is essential. Over 50 years ago, phenylketonuria was diagnosed using a simple screening method that became the prototype for newborn screening. It was found that phenylketonuria, a devastating neurologic disease characterized by intellectual disability and progressive leukodystrophy, could be identified early and treated with diet. The success of early detection and treatment led to universal newborn screening for phenylketonuria. In the United States and internationally, newborn screening has evolved to include screening for an ever-increasing number of neurometabolic and neurogenomic disorders that, if treated early, may manifest improved overall prognosis. As the use of next generation sequencing becomes more widespread and financially viable, the feasibility of using genomic technology as a screening tool in the newborn period is on the horizon. This will bring on enormous opportunities but equally challenging difficulties from interpretation of results to ethical concerns that, as a community, we will need to address.

Key points

 

• Newborn screening has been extremely successful in early detection and diagnosis, allowing for early treatment.

 

• Each state in the U.S. governs its own newborn screening program, testing between 30 and 50 disorders. These disorders are serious, but often treatable.

 

• Four million infants born each year in the U.S. undergo newborn screening.

 

• The Recommended Uniform Screening Panel for Core Conditions is updated periodically by The Advisory Committee on Heritable Disorders in Newborns and Children and can be accessed at the following website: https://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/.

Historical note and terminology

Newborn screening originated in 1963, when Robert Guthrie developed a test for phenylketonuria using heel stick blood samples dried on filter paper (Wilcken and Wiley 2015). Screening programs have since been developed on a state-by-state basis, and disorders have been added based on the Wilson and Jungner criteria, published by the World Health Organization in 1968 (Wilcken 2012). The Institute of Medicine published the following selection criteria for disorders to be added to newborn screening in 1994: 1) the disorder must be a significant problem with a known natural history; 2) each state's Public Health Department must offer further diagnostic testing and follow-up for babies with positive screening results; and 3) effective treatment must be available. The selection criteria were further refined by the American Academy of Pediatrics in 1999: 1) the disorder frequency justifies the cost of screening; 2) the test is simple, safe, precise, validated, and acceptable; and 3) there is available safe and effective treatment (Brosco and Paul 2013).

The U.S. Secretary's Advisory Committee on Heritable Disorders reviews new disorders to include in newborn screening and maintains the Recommended Uniform Screening Panel, which was last updated July 2018. As advancements have occurred in diagnosis and treatment, disorders have been added to the current recommended list, including 35 core conditions and 26 secondary conditions.

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