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Taking Charge of Your Health


Phenylketonuria or PKU is a rare metabolic
disease that can lead to severe brain disorders caused by the accumulation of the amino acid
phenylalanine to toxic levels in the blood and brain. Amino acids are the basic building blocks
that make up proteins. Phenylalanine, or Phe, is one of the essential
amino acids. It is necessary for life, but our bodies can’t
make it; therefore, Phe must be acquired through foods that contain protein. Normally, once Phe enters the body, most of
it is converted to tyrosine by the enzyme phenylalanine hydroxylase. Tyrosine is then turned into neurotransmitters
important for normal brain development and function. PKU is an autosomal recessive genetic disorder
that affects function of the phenylalanine hydroxylase enzyme. The phenylalanine hydroxylase gene is located
on chromosome 12 and over 600 mutations have been described. The degree of enzyme function can vary. When untreated, people with PKU develop symptoms
such as severe intellectual disability, psychiatric disorders, and seizures. A pregnant woman with PKU must pay special
attention to her Phe levels to reduce the risk of Maternal PKU Syndrome that can result
in heart defects, microcephaly, and developmental disability in her baby. In PKU, elevated Phe levels and reduced tyrosine
levels can change the way the brain functions. This is because Phe uses the same transporters
to get across the blood-brain barrier as other amino acids including- tyrosine and tryptophan. Tyrosine is needed to synthesize dopamine
and norepinephrine, and tryptophan is needed to synthesize the neurotransmitter serotonin. As Phe levels rise, it occupies all the transporters,
making it hard for tyrosine and tryptophan to get across the blood-brain barrier. As a result, dopamine, norepinephrine, and
serotonin levels in the brain begin to fall, leading to abnormal brain development and
intellectual disability. Testing for PKU is typically done as part
of routine newborn screening approximately 24 hours after birth. Screening is done by taking a small blood
sample from a heel stick and measuring blood Phe levels by a simple laboratory test. If the screening test shows high levels of
Phe and low blood tyrosine, a different method is used to repeat the measurement of the blood
amino acids and to confirm the diagnosis. First line therapy for PKU is the low Phe
diet. This includes medical foods such as low or
no Phe medical formulas that are a synthetic form of protein and foods modified to be low
in protein. All high protein foods such as meat, fish,
eggs, and dairy are eliminated from the diet. Measured amounts of some grains, vegetables
and fruit are allowed depending upon the individual patient’s tolerance of small amounts of
Phe. Each patient will need to customize the amount
of Phe dietary intake with medical professionals according to their individual needs. In addition to the low Phe diet, two FDA approved
pharmaceutical treatments are now available. Kuvan is a cofactor for phenylalanine hydroxylase
which helps improve the PKU patient’s innate PAH enzyme activity and increase their Phe
tolerance. Kuvan must be used in conjunction with the
low Phe diet. Palynziq can be used in adults with PKU. Palynziq is an enzyme, injected under the
skin every day by the patient that circulates in the blood, metabolizing Phe, and substitutes
for the defective phenylalanine hydroxylase enzyme. Palynziq works well for many adult PKU patients,
but can have serious side effects in some patients. All right, as a quick recap – in PKU, Phe
levels build up and tyrosine levels drop. Symptoms in untreated individuals include
seizures and severe developmental delay. In the US and much of the developed world,
newborns are routinely screened for PKU. Treatment initiated soon after birth is based
on a diet low in Phe that requires the use of an amino acid-based medical food (formula),
severe restriction of dietary natural protein intake, and the ingestion of modified foods
that are lower in protein. Two FDA approved drugs are also available
for the treatment of PKU.

7 thoughts on “Phenylketonuria – causes, symptoms, diagnosis, treatment, pathology

  1. It's so nice to be able to learn about it as it is now tested early as my aunt had it and was to far from treatment when diagnosed and my uncle was one when he was diagnosed it's a cruel genetic disorder as I have watched it do damage on my aunt she lived longer than we expected and my uncle is still going strong with treatment

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