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DNA
Protein
Conclusion
Phenylketonuria
by Zamaan Qureshi and Chinmay Amin
Intro: Phenylketonuria (PKU) is rare genetic disorder which
causes an amino acid, phenylalanine to build up in the body.
PKU is caused by an issue in the enzyme that helps to break
down phenylalanine. The first cases were identified in 1934
when Dr. Asbjørn Følling examined two severely mentally
retarded children. He proved that PKU was responsible for this
by noticing phenylpyruvic in their urine. Phenylketonuria was the
first inborn issue that impacted the mind.
Onset of this disease is usually from birth two 2 years old. In
extreme rare cases, the disease doesn’t appear late into
adulthood. In one case, the disease wasn’t noticed until the
patient was 59 years old. Symptoms “include intellectual
disability (formerly called mental retardation), delayed
development, behavioral, emotional and social problems,
psychiatric disorders, neurological problems that may include
seizures, hyperactivity, poor bone strength, skin rashes
(eczema), a musty odor in the child's breath, skin or urine,
caused by too much phenylalanine in the body, fair skin and
blue eyes, because phenylalanine cannot transform into melanin
— the pigment responsible for hair and skin tone, and an
abnormally small head (microcephaly)” (Mayo Clinic). Prognosis
http://medifitbiologicals.com/phenylketonuria/
Within the first 1-2 days of birth, doctors can test for
Phenylketonuria by taking the blood of the heel of the baby.
for the long term is normal unless there are issues with therapy
or if blood phenylalanine levels rise. Normal life expectancy if no
issues occur.
Location: Chromosome 12 (12q) 12q23.2
Protein: Phenylalanine Hydroxylase (PAH) is an enzyme for
breaking down a part of an amino acid called phenylalanine.
Interestingly, phenylalanine is found in all proteins humans
consume and some artificial sweeteners. On top of this,
Phenylalanine Hydroxylase converts phenylalanine into tyrosine,
which our bodies use to make different variations of hormones,
chemical signals that go to the brain, and a physical feature
called melanin which is a pigment. This is what colors our skin
and hair. Beyond this, if tyrosine s broken down further, it can be
used to produce ATP. Approximately 500 mutations have been
found in the PAH gene, all of these people have PKU. Generally,
the mutations that occur are only single amino acid changes,
however, there are a variation of deletions that have been
identified. A rare kind of mutation in the PAH gene sees that the
actual production of PAH enzyme is incorrect. When these
variations of mutations occur, the processing of phenylalanine is
disturbed. Due to this, phenylalanine builds up in the blood and
tissues, and because of what tyrosine does to help our brain
signals, and because the nerve cells are extremely sensitive, the
phenylalanine builds up and shuts down brain signals. When
untreated, the disease leads to severe brain damage. Other
names of the enzyme Phenylalanine Hydroxylase include…
• L-Phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase
(4-hydroxylating)
• PH4H_HUMAN
• Phenylalaninase
• Phenylalanine 4-Hydroxylase
• Phenylalanine 4-Monooxygenase
• PKU1
http://drustapbio.wikia.com/wiki/Phenylketonuria
This image describes some of the physical features of patients with
Phenylketonuria who are mentally retarded vs normal children.
Inheritance: Autosomal Recessive
https://ghr.nlm.nih.gov/gene/PAH
http://omim.org/entry/612349
Examples of PKU in Patients
1) Mecca, Saudi Arabia (1988)
In the year 1998, in Mecca, Saudi Arabia, there
was a case of PKU involving an ethnically Malay
boy (Initials H.A.R. - no full name given) born
through a fairly normal pregnancy. However, he
showed signs of being abnormal (not being able to
hold his head up for 3 months, or sit without
support for 20 months). He also experienced
changing of hair color, and signs of standard
retardation later in his youth. Many tests did not
show any conventional abnormalities, but through
a chromatography test of his urine, it was
discovered that there was excess Phenylalanine.
He, like many others with PKU, was put on a low
Phenylalanine diet to prevent clotting and further
retardation.
http://www.e-mjm.org/1989/v44n3/phenylketonuria.pdf
PKU Diet
PKU Patients require a specific, low protein diet,
because these foods create high blood PHE levels
and the liver of people with PKU are not able to
break down the acid PHE. Based on research,
PKU patients should have to follow this diet for the
rest of their life in order to ensure that they are fine
even when PHE levels are low.
www.nursebuff.com
https://depts.washington.edu/pku/about/diet.html
PKU Video- https://www.youtube.com/watch?v=XKSoMi4U-1k “Living with PKU with Kevin Alexander”