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PHENYLKETONURIA (PKU)
Phenylketonuria (PKU)
Phenylketonuria (PKU) is characterized as a lack, or deficiency, of the gene,
phenylalanine hydroxylase (PAH), and without proper diet, results in mental retardation and
behavioral abnormalities (Letcher, 2006). Phenylketonuria is characterized as an autosomalrecessive disorder resulting from the mutation of the PAH gene located on the 12th chromosome
pair (Phenylketonuria, 2007). Phenylketonuria, unlike many genetic disorders, offers an effective
source of treatment which requires a protein free diet (Management Guidelines, 2008).
Symptoms are often suppressed or reduced substantially by this unique diet, should it be
established at an early age (Letcher, 2006).
Phenylketonuria is defined as a disorder resulting from an implication in the PAH gene.
This gene is responsible for the production of the phenylalanine hydroxylase, as an enzyme that
breaks down phenylalanine. Subsequently, phenylalanine is eventually converted into tyrosine,
which is crucial to the body (Phenylketonuria, 2008). Statistically, one in every seventy people
of the United States are carriers of phenylketonuria, while one in every 15,000-20,000 are truly
diagnosed with phenylketonuria (What is Phenylketonuria, 2005). In America, this leaves
approximately five million carriers with 15,000 actually suffering from phenylketonuria.
Phenylketonuria is most prominent, in the United States, amongst Caucasian and Native
American ethnicities (Letcher, 2006). Mental retardation and behavioral abnormalities are direct
symptoms, the most prevalent, amongst phenylketonuria patients (What is Phenylketonuria,
2005). These symptoms can be resolved with a treatment requiring a strict diet without protein,
which the body is unable to break down (Letcher, 2006).
Asbjorn Folling (1888-1973), a Norwegian scientist, was the first to effectively conduct
experimentation to truly discover phenylketonuria. In 1934, he conducted research using a pair
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PHENYLKETONURIA (PKU)
of mentally-retarded siblings. Folling found that the siblings’ urine turned a deep green color
once ferric chloride was added to it. He discovered high traces of phenylpyruvic acid in their
urine, accounting for the abnormal color. This led to the discovery of the fact that their body was
not properly breaking down tyrosine, which meant high levels of phenylalanine, and accounted
for their mental disability. Although Folling did not know, specifically, the significance, and
existence, of the PAH gene and phenylalanine hydroxylase in phenylketonuria, he set the basis
for the explanation behind this disease (PKU(Phenylketonuria), 2008).
Phenylketonuria is an autosomal-recessive disorder, meaning that both parents must have
donated a recessive gene and that the abnormality is within the first twenty-two chromosomes,
specifically in the 12th pair (Letcher, 2006), corresponding to the picture provided below (PAH,
2008). If both the mother and the father
carry the recessive gene, they offer a
50% chance of carrying the
phenylketonuria gene to their child.
However, there is only a 25% that the
child will actually suffer from
phenylketonuria. This PAH gene on the twelfth chromosome is responsible for the production of
phenylalanine hydroxylase, which is an enzyme that breaks down phenylalanine. The lack of
phenylalanine hydroxylase allows an unhealthy buildup of phenylalanine, which converts to
tyrosine, and causes severe implications. Research on the genetics within phenylketonuria is not
quite defined and thus leaves scientists hypothesizing that the mutation of the PAH gene either
results from a deletion, insertion, missense mutation, splicing defect, or nonsense mutation.
Scientists speculate at least four-hundred possible mutations or combinations of mutations
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PHENYLKETONURIA (PKU)
resulting in PKU, which are also responsible for hyperphenylalaninemia, a less severe case of
PKU. In hyperphenylalaninemia, symptoms parallel PKU, but are not as heavy as
phenylketonuria (Phenylketonuria, 2007).
At birth, a child may appear as though they do not display symptoms of phenylketonuria,
but gradually, at least within three to five months, permanent and irreversible brain damage
leading to mental retardation is evident (Lerner & Lerner, 2008). These children exhibit a
multitude of behavioral abnormalities. Some are highly stricken from anxiety and suffer from
depression. They avoid eye contact and confrontation (Letcher 2006). Untreated, adults are
highly likely to suffer from autism or agoraphobia, or severe anxiety. Children can also show
symptoms of the exact opposite: hyperactivity with impulsive behavior and talkativeness. These
symptoms often lead one to become an anti-social being and cause the child to grow up disobedient, often lying, and bullying (Lerner & Lerner, 2008).
Brain damage is the most common symptom of phenylketonuria and is often irreversible
by the age of one, should proper treatment not be taken. Low IQs are common within those
suffering from phenylketonuria also associated with learning disabilities and inabilities to
concentrate (Letcher 2006). Patients also suffer from impaired memory and a high likelihood of
seizures. People with phenylketonuria also differ in their physical appearance. Their high
phenylalanine levels cause strange-smelling urine and sweat, explained the excess levels of
phenylpyruvic acid being excreted by the body. They are also characterized as having lighter
hair, skin, or eye color. Those suffering from phenylketonuria are also likely to have Eczema
(Lerner & Lerner, 2008).
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PHENYLKETONURIA (PKU)
The only available, current treatment for phenylketonuria requires a diet free of any food
high in protein. Foods categorized as high in protein include meat, fish, dairy products, and
poultry. Along with these restrictions, they must constantly monitor their phenylalanine levels
within their bloodstream (Management Guidelines, 2008). People suffering from
phenylketonuria can moderate foods with moderate levels of protein such as potatoes and grains.
As patients become older, they can gradually include foods with a low amount of protein into
their diet, but at a controlled amount. Because phenylketonuria is a life-long condition, this diet
must be kept for life. Even patients who have not been on the diet for their entire life claim to
feel as though their symptoms are lessened/treated with the diet (Letcher, 2006).
Currently, the protein-free diet stands as the only source of treatment for phenylketonuria.
However, this treatment is highly effective, especially when applied at birth. Because the PAH
gene of the 12th chromosome has not been detailed specifically to account for what causes
phenylketonuria, little understanding of phenylketonuria leaves the special diet as the only
solution. The brain damage caused from phenylketonuria is irreversible and little testing has been
conducted in order to treat the mental aspects to phenylketonuria. Otherwise, no future treatment
really stands open for phenylketonuria researchers (Letcher 2006).
From Folling’s basic discovery of phenylpyruvic acid in urine (PKU(Phenylketonuria),
2008) to the discovery of the PAH gene (Letcher, 2006), understanding of phenylketonuria has
increased and allowed for proper treatment. Phenylketonuria has truly come a long way as far as
treatment, with the special diet, and hopefully medical and technological advancements will
allow for the reversal of the symptoms in the future. Until then, early diagnosis applied with
proper treatment seems to be the only, as of now, and best method of relieving symptoms of
phenylketonuria.