Sign Up for a Free Account
  • Updated 03.27.2024
  • Released 04.09.2015
  • Expires For CME 03.27.2027

Screening of newborns for neurogenetic abnormalities



As we move into the era of personalized therapies for rare diseases, understanding the history and evolution of newborn screening for neurologic disorders 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 neurogenetic disorders that, if treated early, may lead to improved prognosis and overall functional outcome. Next generation sequencing, which was previously a novel genomic technology, will likely become an increasingly important part of newborn screening. Unfortunately, the discovery of neurogenetic disorders using next generation sequencing has outpaced the development of disease-modifying therapies, which is a hallmark principle of newborn screening. Use of these technologies has enormous promise, but there are ethical implications and difficulties with results interpretation that must be considered.

Key points

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

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

• The Recommended Uniform Screening Panel (RUSP) 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: There are currently 37 core and 26 secondary conditions on the RUSP.

• Although the RUSP is a recommendation, each state in the U.S. governs its own newborn screening program, testing between 30 to 50 disorders.

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 (58). 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 (57). 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 (11).

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 January 2023. As advancements have occurred in diagnosis and treatment, disorders have been added to the current recommended list, including 37 core conditions and 26 secondary conditions.

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, including video clips of neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of neurology in 1,200 comprehensive articles.

  • Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660



ISSN: 2831-9125