Pku GRP 1
Pku GRP 1
Pku GRP 1
Phenylketonuria (PKU)
Aubrey Aligam
Lyra Jade Amparo
Jersey Mari Arante
Kieth James Balagon
Nica Banayo
Maria Jericka Basañes
Jennica Banzuela
Kc Cassandra Butalon
Stephen Torilllas
BSND 1- 1D
August 2019
I. Introduction
Over fifty years ago, a simple screening test for PKU was developed by Dr. Robert
Guthrie, which became the prototype for universal newborn screening. In 1970, it
become a routine in every industrialized nation to conduct new born screening for PKU,
and had even extended to third world countries. Phenylketonuria is very rare that the
disease affects only one in fifteen thousand people but it became widely known because
it is a victory for scientific medicine.
In PKU, the gene responsible for producing phenylalanine hydroxilase, the enzyme
that converts one amino acid (phenylalanine) to another (tyrosine) is defective.
Therefore, the body becomes deficient in tyrosine and phenylalanine accumulates in the
blood. This eventually causes imbalance that inhibits protein synthesis in the brain,
which n turn results in severe neurological symptoms or mental retardation.
The severity of PKU varies. Classic PKU is the most severe form of the disorder.
High levels of phenylalanine accumulate in the blood because the enzyme responsible
for converting phenylalanine to tyrosine is absent or severely reduced. This condition
results to severe brain damage. In mild and moderate (or variant) form of PKU, there is
a smaller risk of brain damage because phenylalanine levels are not as high since the
enzyme retains some function. Hyperphenylalaninemia is the most minor type where
phenylalanine has the lowest level above normal.
Initially, symptoms o PKU is not visible on newborns but without treatment, the
sign of PKU like reversible brain damage and marked intellectual disability, begin to
develop within the first few months of the baby. In children and adults, a stale odor in the
breath, skin, or urine, neurological (seizures and tremors), behavioral, emotional and
social problems are signs and symptoms that can be observed when the PKU was
remained untreated. In mothers with PKU, high blood phenylalanine levels during
pregnancy can lead to fetal birth defects or miscarriage problems.
Protein-rich foods (milk, cheese, nuts or meat), aspartame (an artificial sweetener)
and even grains (bread and pasta) help in the accumulation of phenylalanine in the
blood which results in damage to nerve cells in the brain. This is why, people with
PKU—babies, children and adults—need to follow a diet that limits phenylalanine, for
the rest of their lives.
This paper aims to inform individuals, raise awareness to the public and clarify
misconceptions about the genetic disorder, Phenylketonuria. Specifically, it sought
answers to the following questions:
This study targets a wide range of people including the community, colleges and
universities, government, medical health professionals and future researchers. Since
this is not a research paper, this focuses only on what the target readers have to know
about phenylketonuria. This includes the history, types, causes, signs, symptoms and
treatment of the disease. The enzyme phenylalanine hydroxylase and amino acids such
as phenylalanine and tyrosine were mentioned to give a more complex reason of how
the disease occurs. Genetic screening and pre-natal diagnosis were briefly discussed.
Other health problems related to the disease were also mentioned though they were not
elaborated because the focus of this term paper is on the disease.
The availability of reference books, journals, articles and online sources set a limit
to the data that was gathered. Being a very rare genetic disorder, studies and articles
about phenylketonuria is not as numerous as those that discuss about other diseases.
II. Review of Related Literature
According to the Genetic Science Learning Center (2018), "A genetic disorder is a
condition that is caused by an abnormality in an individual's DNA.", flaws found within
the DNA may be in a single-base mutation in a single gene or it may also be additional
chromosomes or lack thereof (General Science Learning Center, 2018). Genetic
disorders regarding cognitive abilities ranges from dyslexia to autism (Tager-Flusberg,
H., 1999), while genetic disorders regarding metabolism ranges galactosemia to maple
sugar urine disease (Lee E., 2017). Both metabolism and cognitive genetic disorders
are found in Phenylketonuria.
PKU has no known current treatment and is managed solely through restrictions in
the diet; said treatment may lead to certain complications. Furthermore, medical
advancements have been made in improving food and its palatability (Christodoulou, J.
& Hafid, N., 2015). Even mothers, who are diagnosed with PKU, go through a low-
phenylalanine diet. Neonates, who are born to mothers of PKU who no longer follow the
said diet, have a higher risk of developmental delay due to the high exposure of
phenylalanine before birth (Committee on Genetics, 2008).
Gene therapy is a new type of PKU treatment that is still undergoing certain tests
on mice before being presented to the public. This is done by using novel adeno-
associated virus vectors to supplement a non-mutated PAH gene into the liver of a PKU
mice; this is said to restore activities in the liver and lower blood Phe. Yet, the gene
therapy is observed to only have temporary effects and reinjection of the said vector
leads to its damage by antibody-mediated immune reactions (Concolino, D.
&Strisciuglio, P., 2014).
In order for an amino acid to pass through the blood brain barrier, it requres a
transporter protein (Bhatia, G., 2006). Large neutral amino acids (LNAA) are available in
the market. This treatment involves LNAA blocking Phe from entering the brain. Due to
the blocked passage, Phe may not enter the brain, which will result in lower levels of
Phe found in the brain; introducing LNAA in a Phe-restricted diet will do this. On the
contrary, this is not a permanent solution to the Phe-restricted diet, yet it is a good
supplement for those who are poor in diet control (National PKU Alliance, 2019).
III. Methodology
A. Identification
Dr. Robert Guthrie was responsible for a screening test that helped detect
Phenylketonuria—this happened 50 years ago. This is a known victory for medicine as
newborns all appeared normal, only later in life will they show certain disorders and by
then, much damage has already occurred and could be considered as irreversible.
Currently, this test is known as newborn screening. This is a mandatory test done to
neonates to detect for any congenital metabolic disorders. Said disorders may cause
severe mental retardation or death if not treated at an early stage. A newborn screening
test is composed of:
Obtaining a few drops of blood done by pricking the heel of the neonate.
A hearing test
Measuring the oxygen level in the blood
In terms of diagnosis, an untreated PKU child at 3-6 months will eventually lose
their interest with their environment. At 1 year old, that child will appear as mentally
retarded and their skin is noticeably fairer than their siblings or someone without PKU.
Other symptoms of PKU are:
Behavior disorders,
Seizures,
Slow development or growth,
Eczema,
Microcephaly, and
Offensive or musty urine and skin odor
B. Research Design
This study made use of descriptive method of research to be able to come up with
adequate information regarding the genetic disorder, Phenylketonuria. Descriptive
method was used because it was designed to present facts concerning the nature of
any phenomena. It helps in collecting large amount of data to have a more focused,
detailed and accurate interpretation of findings. Also, it helps in providing answers to the
questions of what and how of this study.
C. Data Gathering
Since the research study is in a qualitative approach, the students used a non-
probability sampling technique, specifically, convenience sampling wherein published
articles or documents are properly gathered through the use of the internet that will
eventually lead the students have an organized and reliable sources for the said topic.
The students preferred using a convenience sampling simply because it is reasonable,
and the collection of datum can be done in a short period or duration of time.
Electronic medias had greatly provide an extension of data that the researchers
will analyze and further explain. Also, the students collected data by the utilization of
document analysis and combined different sets of informations gathered by distinct
sources to make a general awareness along with expanded comprehensions in order to
mainly achieve the aims or objectives of the study that will surely help the readers
apprehend the particular research topic, which is the Phenylketonuria or PKU.
III. Results and discussion
This part of the term paper presents and discusses the findings, analysis and
interpretation of the data and information gathered pertinent to the comprehension of the
objectives of the study, which was to raise awareness or clarify misconceptions about
the genetic disorder, phenylketonuria or PKU. Specifically, to sough answers or
explanations about the significant informations about PKU, its types, signs and
symptoms, how is it acquired, procedures done to detect it and lastly, its treatment plans
or possible medications to prevent severe health problems caused by Phenylketonuria
or PKU.
Phenylalanine is an amino acid that babies are incapable of breaking and will
eventually precede to a rare condition called Phenylketonuria (PKU). This inherited
disease, which means it is rendered down through the genes of the mother and father;
is caused by mutations in the gene that abet the formation of an enzyme called
phenylalanine hydroxylase. This enzyme alleviates the atomization of phenylalanine and
when this gene does not generate accurately or its levels escalated, the body can’t
disrupt phenylalanine that can antecedent damage to nerve cells in the brain, which
could direct to cognitive and developmental dysfunction.
The third type is known for having slighter critical configurations while having levels
not stunted but also not elevated and is called as moderate, variant or non-PKU
hyperphenylalaninemia. Aside from that, people infected with this type of PKU has a
little probability of brain destruction and may not necessitate treatment with a low-
Phenylalanine diet, but still need to follow a particular diet to avoid cognitive disabilities.
Furthermore, most country in the United States entail a screening test or a simple
blood test as a segment of the newborn screening panel to easily perceive PKU. This
test is mainly done by taking a small drops of blood from the baby prior to when the
baby leaves the hospital. Also, blood and urine tests are in need to assert in diagnosis if
the screening went positive.
The phenylalanine level builds up in the baby’s blood and again, can cause brain
damage, seizures and cognitive disability. If a baby’s body is impotent to enzyme that
converts phenylalanine into another amino acid, it may known to be as tyrosine.
In Canada and the United States, babies are tested for PKU wholly right after birth
and as mentioned, this disease is very significant to remark untimely. As stated at the
HealthLinkBC website, PKU’s blood sample is conventionally seized from the baby’s
heel or heel stick and the first few days after birth is when it is tested or as early as 24
hours after birth. In some quarter, these tests may be sustained within the first week or
two after birth.
On top of that, newborns are tested consistently for PKU at birth even if they are
born infected and again, signs and symptoms of PKU may not be detectable for a few
months. Besides, the harm caused by PKU can undertake weeks after the baby has
established drinking breast milk or formula.
However, when PKU is not diagnosed at birth and treatment does not begin
ahead of time, babies will eventually flourish signs and symptoms of PKU within few
months. These signs and symptoms mentioned in young babies include:
Moreover, uncontrolled PKU can progress to other difficulties as the child grows,
such as:
Intellectual disability
Developmental delays
Problems with memory
Irritability
and
Behavioral, emotional and
social problems
Hyperactivity
When people with PKU appositely cope their diet normally don’t manifest
symptoms and at one time a particular diet and supplementary treatments got under
way, manifestations will eventually begin to shrink.
A person with PKU must remain on diet and proceed a strict low-Phenylalanine
diet or a diet that bound foods with phenylalanine, both prior to becoming pregnant or
throughout pregnancy for better corporeal and intellectual health. Additionally, foods
with high-protein should also be circumvented, such as milk, cheese, eggs, meats, nuts,
legumes, tofu, and so on. People with PKU are also required to evade the sweetener
aspartame (which is found in medications, vitamins, foods and drinks), because it
liberates phenylalanine when assimilated that will finally source to increase the extent of
phenylalanine in a person’s blood. In often times, people with PKU have to restrict their
consumption of lower-protein foods, like certain fruits and vegetables. However, low-
protein noodles and other special products can be incorporated in PKU diet.
Furthermore, the PKU diet is not that easy and can be very exacting. An
assistance inclined from family and friends or a support group can be beneficial and
sticking or focusing with an established diet fortifies better functioning and ameliorate
overall health.
According to Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), the U.S. Food and Drug Administration (FDA) has authorized
the drug sapropterin dihydrochloride (Kuvan®) for the treatment of PKU. It is a
manifestation of BH4 (an essential cofactor for countless enzymes in the body, involving
those required in the configuration of nitric oxide (NO), and the key neurotransmitters
dopamine, serotonin and epinephrine) which aid the body to break down phenylalaine
and participates a critical part in both heart and cognitive health. However, one ground a
person may not break down phenylalanine is having a small amount of BH4.
Additonally, Kuvan® only abet people diminish the phenylalanine in their blood
and it will not minimize the phenylalanine to the appropriate amount even if medication
helps, that is why it must be utilized simultaneously with the PKU diet.
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