Download MPH 510-Phenylketonuria

Amanda Fox
MPH 510-Capstone Project
Phenylketonuria
Phenylketonuria (PKU) is a rare metabolic disorder that occurs when the body is not able
to utilize the amino acid phenylalanine. “PKU is usually the result of autosomal recessive
disorders caused by mutations in the phenylalanine hydroxylase gene” (Hellekson, 2001).
Amino acids are the backbone of protein and are found in the foods we eat. The liver produces
an enzyme phenylalanine hydroxylase (PAH). PAH usually converts phenylalanine to another
amino acid, tyrosine. Without the enzyme PAH, phenylalanine will accumulate in the blood and
body tissues. When this occurs, the excess phenylalanine becomes a toxin to the central nervous
system. “Untreated PKU is associated with an abnormal phenotype which includes growth
failure, poor skin pigmentation, microcephaly, seizures, global developmental delay and severe
intellectual impairment” (Williams, Mamotte and Burnett, 2008). Early screening, diagnosis and
treatment are crucial in order to prevent the development of serious health risks.
PKU affects around 1 in 10,000 to 1 in 20,000 depending on location throughout the
world. In the United States, approximately 1 in 13,500 to 19,000 infants are born with PKU.
The incidence of PKU also varies with ethnicity. There is a higher prevalence of PKU found in
Caucasians and Native American’s than African Americans (Lindegren ML, Krishnaswami S,
Fonnesbeck C, et al., 2012). Throughout the country, every infant born is now tested for PKU so
there is no specific location screening is higher; it is done everywhere.
Screening processes for PKU started back in the 1960’s. Screening consists of taking
neonatal blood samples from a prick of the heel during the first days of the newborns life. The
blood is evaluated for abnormally elevated levels of phenylalanine. “The three main laboratory
methods used to screen newborns for PKU are the Guthrie bacterial inhibition assay,
fluorometric analysis and tandem mass spectrometry” (Hellekson, 2001). In order for effective
screening to take place, many steps are taken; specimen collection, specimen transport and
tracking, laboratory analysis, data collection and analysis, locating and contacting families of
infants with abnormal results, diagnosis, treatment, and long term management- psychological,
nursing and social services, medical nutritional therapy and genetic family counseling.
PKU can also be inherited if parents have PKU or both carry the recessive gene that
causes dysfunction in the PAH enzyme. Genetic testing can be done to see if parents are carriers
of the non-working PAH enzyme. This is done simply through a blood sample from each parent.
This blood sample can look at changes in the pair of genes that causes PKU (STAR-G, 2012).
This testing can be done while the woman is pregnant or right after the baby is born. If a woman
is known to have PKU and becomes pregnant, she must take special consideration of diet as well
as regularly checking up with her doctor to monitor her levels of phenylalanine.
PKU tests, as many other tests, have their positives and negatives as far as accuracy. The
main test done to test for PKU is called the Guthrie test. There have not been well designed
evaluations on the sensitivity and specificity of this test, though. Studies that have looked at the
Guthrie test look at how many babies have been tested with this specific test and the accuracy
rate of diagnosing PKU. They have found that false-negative results are extremely rare. Most
missed cases of PKU are not due to false-negative results, rather inadequate submissions of
samples, clerical error involving the sample, or failure to follow up with positive results
(Baldwin & Wilson, 2012). False-positives can occur in PKU screening. The ratio found
between false-positives to true-positives is as high as 32 to 1.8. That number is high and can
cause anxiety in patients if recalled to take a second test.
When looking at the sensitivity and specificity of the screening tests, experts have found
that the sensitivity is greatly affected by age of the infant. Screening that is done between the
first day or two of life has been found to yield a low sensitivity due to the blood level of
phenylalanine being normal. This is because the initiation of protein feedings starts when the
baby is born so the levels do not have time to rise until after the first day or two. These infants
who were known to have higher rates of PKU were tested as false-negative if tested within the
first 24 hours of life. The false-negative rates decreased significantly on day two and three; from
2% to 31% on day one to .6% to 2% on day two and .3% on day three. Currently, nine of fiftythree screening programs have changed the cutoff value to define abnormal which improves
sensitivity at the expense of specificity (Baldwin & Wilson, 2012).
There are some ethical considerations to be looked at when it comes to PKU testing for a
public health professional’s perspective. Genetic screening is a sensitive topic. Some people
feel genetic screening may lead to discrimination of individuals who possess “inferior” genes. It
is known that employers and some insurance companies want to asses people based off of their
genetic composition. This means that some individuals may be denied insurance or even a job if
they are diagnosed with some type of genetic disease and in this case, PKU. Also, another
argument is that genetic screening could lead to reproductive decisions based off of the genes of
the child. Some people decide to abort babies if they find out there are genetic discrepancies.
When it comes to PKU, if diagnosed early, treatment can eliminate symptoms so it is not as
severe as other genetic abnormalities but it still could set off some ethical issues if parents do not
want the diagnosis of their child put out in public. As always with children, an informed consent
must be signed and the parent must be willing to do the test.
I find PKU testing to be very helpful, especially because with early diagnosis, treatment
is easy and almost 100% beneficial. All babies get tested for PKU when they are born to
eliminate mental retardation and other health effects if they are diagnosed. I like that this is
being done in hospitals around the country to prevent children from having abnormal lives. I
would continue using the Guthrie test because it is very accurate and helpful. There are some
ethical issues involved, but the positives greatly outweigh the negatives when it comes to
screening. Most people agree to have their babies tested when they are born just because PKU is
easily fixed with diet and regular blood tests to make sure levels of phenylalanine are not too
high in the system. Educating people on this topic is a key factor in making sure every baby gets
tested when they are born.
References
Baldwin, R. & Wilson, M. (2012). Screening for phenylketonuria. Retrieved on February 27,
2013, from http://odphp.osophs.dhhs.gov/pubs/guidecps/text/ch44.txt.
Hellekson, K. (2001). NIH consensus statement on phenylketonuria. American Family
Physician, 6(7), 1430-1432. http://www.aafp.org/afp/2001/0401/p1430.html.
Lindegren ML, Krishnaswami S, Fonnesbeck C, et al. (2012). Adjuvant treatment for
phenylketonuria (PKU). Retrieved on February 23, 2013 from
http://www.ncbi.nlm.nih.gov/books/NBK91338/.
STAR-G. (2012). Amino acid disorders. Retrieved on February 26, 2013, from
http://www.newbornscreening.info/Parents/aminoaciddisorders/PKU.html.
Williams, R., Mamotte, C., & Burnett, J. (2008). Phenylketonuria: an inborn error of
phenylalanine metabolism. The Clinical Biochemist Review, 29(1), 31-41.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423317/.