Screening of newborns for neurogenetic abnormalities

Amy Goldstein MD (Dr. Goldstein of Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, received consultant fees from Stealth Biopeptides and Biomarin.)
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 March 10, 2017; expires March 10, 2020


Over 50 years ago, phenylketonuria was diagnosed using a simple screening method that became the prototype for newborn screening. Phenylketonuria, a devastating neurologic disease with intellectual disability and progressive leukodystrophy, could be identified early and treated by 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 neurogenetic disorders that, if treated early, may manifest improved overall prognosis.

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.


• Even when biochemical and genetic studies are positive, the genotype-phenotype correlation remains unknown for some disorders, leading to ethical considerations and difficulty in follow-up and counseling.


• 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:

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 developed on a state-by-state basis. Disorders have been added based on 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).

With improvements in high throughput technology such as tandem mass spectrometry and high-performance liquid chromatography, the number of disorders included in newborn screening programs has risen to about 31 core disorders and 26 secondary disorders. 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. As advancements have occurred in diagnosis and treatment, disorders have been added or are in discussion. One recent initiative has been to include many of the lysosomal storage disorders to newborn screening. Treatments have emerged, including enzyme replacement therapy, hematopoietic stem cell transplant, and substrate reduction therapies (Brosco and Paul 2013).

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