Phenylketonuri

a Disorder
History of
Phenylketonuria
(PKU)
• It was first described by Asbjörn Fölling in 1934 in Norway. PKU
has been the paradigm of inherited metabolic disorders.
• In 1934 at Rikshospitalet, Følling saw a young woman
named Borgny Egeland. She had two children, Liv and
Dag, who had been normal at birth but subsequently
developed intellectual disability. When Dag was about a
year old, the mother noticed a strong smell to his urine.
Følling obtained urine samples from the children and,
after many tests, he found that the substance causing
the odor in the urine was phenylpyruvic acid. The
children, he concluded, had excess phenylpyruvic acid
in the urine, the condition which came to be called
phenylketonuria (PKU).
• It also allowed the proposition for the first biochemical
explanation of mental retardation.
• This prompted the widespread search of this condition in
neonates through newborn screening.
Understanding PKU

It occurs due to a buildup of phenylalanine in the body.

Phenylalanine is an essential amino acid present in a number of

different foods like fish, pork and cheese.

Patients with PKU lack a gene which codes for the genetic
information needed to synthesise phenylalanine hydroxylase
which breaks down the amino acid, phenylalanine.
 • The incidence of PKU is approximately 1 in 10,000 in
European populations
• High prevalence rates  Italy, Ireland and Turkey
• Estimated rates in turkey are said to be 1 in 4000
Epidemiolog live births
y of PKU • Less common in the African-American population,
with an incidence of approximately 1 in 50,000
• PKU is rare in Finland as well as Japan, although its
incidence may vary markedly between different
regions.
• Equally frequent in males and females
 Biochemical • It is an autosomal recessive disorder usually
basis of PKU caused by the deficiency of the hepatic
enzyme phenylalanine hydroxylase (PAH).
• PAH catalyses the hydroxylation of
phenylalanine to tyrosine, the rate limiting
step in phenylalanine catabolism.
• The enzyme deficiency leads to the
accumulation of phenylalanine resulting in
hyperphenylalanaemia which is the increased
phenylketones and a decrease in myelin
formation, dopamine, norepinephrine and
serotonin production
Clinical symptoms of PKU • The most severe form of the disease is
called classic PKU. Here, the child will
appear normal in the first few months of
their life but will later, without treatment,
develop symtoms such as:
• Seizures
• Tremors
• Stunted growth
• Skin conditions e.g. eczema
• Musty odour of breath, skin or
urine

• If left undiagnosed this could lead to

• irreversible brain damage and
intellectual disabilities within the
first few months of life
• behavioral problems and seizures
in older children
Clinical symptoms of PKU • A less severe form of PKU is called
variant PKU or non-PKU
hyperphenylalaninemia  when the
baby has too much phenylalanine in
their body
• may have only mild symptoms
but are still required to follow
a special diet to prevent
intellectual disabilities.
• Once a specific diet and other
necessary treatments are started,
symptoms start to diminish. People
with PKU who properly manage
their diet usually don’t show any
symptoms.
 • There is no cure for PKU but a diet that limits
Treatment of food with phenyalanine is the most important
treatment for the disorder  diet low in protein
PKU • Newborns diagnosed with the disease must use
special infant formula. This can be mixed with
small amounts of breast milk or regular formula.
Babies do need some phenylalanine for normal
development, however, too much can be harmful
.
 Since PKU is a genetic condition, it
cannot be prevented or avoided.
Genetic testing is the only way to
determine if people carry the
defective gene which can, in turn, help
provide adequate treatment options
at an early stage to minimise
symptoms as much as possible.
Bibliography

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• The Medical Biochemistry Page. 2022. Phenylketonuria: PKU - The Medical Biochemistry Page. [online] Available at:
<https://themedicalbiochemistrypage.org/phenylketonuria/> [Accessed 8 May 2022].
• Genome.gov. 2022. About Phenylketonuria. [online] Available at:
<https://www.genome.gov/Genetic-Disorders/Phenylketonuria#:~:text=Gene%20alterations%20(mutations)%20in%20the,in%20the
%20bloodstream%20and%20body.> [Accessed 8 May 2022].
• nutritionfact.in. 2022. Phenylketonuria (PKU)- Treatment, Prevention, Dietary management. [online] Available at:
<https://www.nutritionfact.in/nutrition-facts/phenylketonuria-pku-treatment-prevention-dietary-management> [Accessed 8 May 2022].
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