This recommendation statement was first published in the Annals of Family Medicine.

Importance: PKU is an inborn error of phenylalanine metabolism that occurs in from 1 per 13,500 to 1 per 19,000 newborns in the United States. In the absence of treatment during infancy, most persons with this disorder will develop severe mental retardation.^1,2

Detection: Two approaches, fluorometry and tandem mass spectrometry, are in common use. The sensitivity and specificity of fluorometry are 100% and 51%, respectively, and of tandem mass spectrometry, 100% and 98%, respectively.³

Benefits of Detection and Early Treatment: There is good evidence that detection by neonatal screening and early treatment of PKU substantially improve neurodevelopmental outcomes for affected persons.

Harms of Detection and Early Treatment: False-positive tests could generate considerable parental anxiety.

USPSTF Assessment: The USPSTF concludes that there is high certainty that the net benefit is substantial for screening for PKU in newborns.

Patient Population

This recommendation applies to newborns.

Screening Tests

Screening for PKU is mandated in all 50 states, though methods of screening vary. There are three principal methods used for PKU screening in the United States: the Guthrie Bacterial Inhibition Assay (BIA), automated fluorometric assay, and tandem mass spectrometry. Screening tests are most accurate if performed after 24 hours of life but before the infant is 7 days old.

Treatment

It is essential that phenylalanine restrictions be instituted shortly after birth to prevent the neurodevelopmental effects of PKU.

Timing of Screening

Infants who are tested within the first 24 hours after birth should receive a repeat screening test by 2 weeks of age. Premature infants and those with illnesses should be tested at or near 7 days of age, but in all cases before newborn nursery discharge.

In 1996 the USPSTF reviewed the evidence for screening for PKU in newborns and found that the benefits substantially outweighed the harms of screening. The benefits of screening for PKU continue to be well established. This update focused on a search for new and substantial evidence on the benefits and harms of screening.⁴ The USPSTF found no new substantial evidence on the benefits and harms of screening for PKU and therefore, reaffirms that clinicians should screen for PKU in newborns. The 1996 recommendation statement, the 1996 evidence report, and the summary of the updated literature search can be found at http://www.uspreventiveservicestaskforce.org.

According to the American Academy of Pediatrics, PKU screening should occur in newborns older than 24 hours and younger than 7 days. Infants screened before 24 hours of life should be re-screened by 2 weeks of age to detect possible missed cases. All infants should be screened at the time of nursery discharge or transfer regardless of age. Sick infants and premature infants should be screened by 7 days of age, regardless of feeding history or antibiotic treatment.⁵ The American Academy of Family Physicians strongly recommends that physicians screen neonates for phenylketonuria.⁶ The American College of Medical Genetics recommends that PKU screening be mandated as part of state newborn screening programs.⁷

Ned Calonge, MD, MPH, Chair, USPSTF (Chief Medical Officer and State Epidemiologist, Colorado Department of Public Health and Environment, Denver, CO); Diana B. Petitti, MD, MPH , Vice-chair, USPSTF (Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Sierra Madre, CA); Thomas G. DeWitt, MD (Carl Weihl Professor of Pediatrics and Director of the Division of General and Community Pediatrics, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH); Leon Gordis, MD, MPH, DrPH (Professor, Epidemiology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD); Kimberly D. Gregory, MD, MPH (Director, Women's Health Services Research and Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA); Russell Harris, MD, MPH (Professor of Medicine, Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, NC); George Isham, MD, MS (Medical Director and Chief Health Officer, HealthPartners, Minneapolis, MN); Michael L. LeFevre, MD, MSPH (Professor, Department of Family and Community Medicine, University of Missouri School of Medicine, Columbia, MO); Carol Loveland-Cherry, PhD, RN (Executive Associate Dean, Office of Academic Affairs, University of Michigan School of Nursing, Ann Arbor, MI); Lucy N. Marion, PhD, RN (Dean and Professor, School of Nursing, Medical College of Georgia, Augusta, GA); Virginia A. Moyer, MD, MPH (Professor, Department of Pediatrics, University of Texas Health Science Center, Houston, TX); Judith K. Ockene, PhD (Professor of Medicine and Chief of Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA); George F. Sawaya, MD (Associate Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences and Department of Epidemiology and Biostatistics, University of California, San Francisco, CA); Albert L. Siu, MD, MSPH (Professor and Chairman, Brookdale Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY); Steven M. Teutsch, MD, MPH (Executive Director, Outcomes Research and Management, Merck & Company, Inc., West Point, PA); and Barbara P. Yawn, MD, MSPH, MSc (Department of Research, Olmsted Medical Center, Rochester, MN).

*Members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to here.

Source: U.S. Preventive Services Task Force. Screening for phenylketonuria (PKU): U.S. Preventive Services Task Force reaffirmation recommendation statement. Annals of Family Medicine 2008;6(2):166. Available online at http://www.annfammed.org/cgi/content/full/6/2/166/DC1.

This document is in the public domain within the United States.

Requests for linking or to incorporate content in electronic resources should be sent via the USPSTF contact form.