Home > Newborn Disorders > PKU
PKU
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.95% [Schulze: 2003]Overview
Deficiency of phenylalanine hydroxylase (PAH), the enzyme responsible for converting phenylalanine to tyrosine, results in accumulation of phenylalanine (Phe) with toxic effects on brain development.Prevalence
PKU occurs in about 1/10,000 live births in the US. [Schulze: 2003] The incidence varies greatly in other populations: Turks - 1/2,600; Irish - 1/4,500; African - 1/100,000; Japanese - 1/143,000; Finnish and Ashkenazi Jewish - 1/200,000. [PKU (GeneReviews)]Maternal and Family History
There are variant forms with minimal elevations of phenylalanine levels (maximal plasma phenylalanine <300 micromolar, bening phenylketonuria) causing no symptoms and requiring no therapy or forms in which phenylalanine levels are only mildly increased (maximal plasma phenylalanine 360-1000 micromolar, mild phenylketonuria) requiring that are usually easy to control with diet and respond to therapy with sapropterin. Children born to women with PKU are at risk for "maternal PKU" because high levels of phenylalanine are teratogenic.Elevated phenylalanine levels can be caused by defects in the synthesis or recycling of tetrahydrobiopterin, an essential co-factor of phenylalanine hydroxylase. Since tetrahydrobiopterin is also a cofactor of other ezymes involved in neurotransmitter synthesis, these patients need to be identified as soon as possible to start appropriate therapy.
Clinical Characteristics
With treatment by early introduction and maintenance of special diet, normal IQ and development can be expected. Without treatment, patients with Classic PKU have no symptoms at birth, but usually develop them by 6 months of age.Initial symptoms may include:
- a musty or "mousy" odor of the body and urine;
- developmental delays in sitting, crawling, and standing; and
- microcephaly.
If patients remain untreated they may develop:
- decreased skin and hair pigmentation (due to lack of tyrosine);
- eczema;
- seizures; and
- profound mental retardation.
Dietary treatment consisting in a diet low in protein and phenylalanine needs to be continued for life. The diet needs to be supplemented with tyrosine that becomes an essential amino acid in this condition. With relaxation of diet, patients have increased incidence of deficits in executive function, attention deficit disorder and school problems. Some patients respond to therapy with tetrahydrobiopterin, the cofactor of phenylalanine hydroxylase that stimulates residual enzyme activity in responsive mutant enzymes.
Follow-up on positive screening test
Quantitative plasma amino acid analysis, red blood cell DHPR assay; urine neopterin profile (the latter two tests to exclude defects in tetrahydrobiopterin synthesis or recycling); DNA testing for PAH gene mutations.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for any concerning symptoms;
- Provide urgent treatment/referral for any significant symptoms or seizures (see the ACT Sheet for PKU (ACMG)
(
351 KB)
for additional information);
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
If the diagnosis is confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see PKU info for parents (STAR-G));
- Support initiation and maintenance of phenylalanine-restricted diet and supplementation of tyrosine and essential amino acids;
- Avoiding the sugar substitute aspartame ("Nutrasweet", "Equal", "Sweetmate", Canderal") in diet drinks and medications;
- Regular blood and urine tests to monitor Phe levels and diet may be indicated;
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management.Resources
Information & Support
For Professionals
PKU info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
ACT Sheet for PKU (ACMG)
( 351 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
PKU (GeneReviews)
Excellent review by John J. Mitchell, MD and Charles R. Scriver, MD including clinical description, differential, management,
genetic counseling, molecular genetics, and a bibliography.
Resources for PKU (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions
screened for.
For Parents and Patients
Support
PKU Listserv
Share ideas and concerns with other PKU parents.
General
PKU info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about PKU and
links to other sites including parent support groups.
PKU (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
National Urea Cycle Disorders Foundation
The National Urea Cycle Disorders Foundation, a non-profit organization, provides support services and information for families;
medical lectures on urea cycle disorders; nutrition and medication resources; and information about events and conferences.
Patient Education
What is Phenylketonuria (PKU)? Genetic Science Learning Center - University of Utah
A brief educational overview of the genetics of phenylketonuria (PKU) from the Genetic Science Learning Center at the University
of Utah.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for PKU: review articles over the last 5 years
Page Bibliography
Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome,
and implications.
Pediatrics.
2003;111(6 Pt 1):1399-406.
PubMed abstract