4. - It was discovered by the Norwegian
physician Asbjørn Følling in 1934.
- It is called Følling’s disease
- He discovered the disease when he
tested the urine of two brothers when he
found benzaldehyde and benzoic acid
5. 1934 Dr Asbjørn Følling firsts describes
phenylketonuria
1937 Dr George Jervis identifies a mutated
enyzyme as the cause of PKU
1951 Professor Horst Bickel develops the first
effective treatment of PKU
1957 Dr. Willard Centerwall develops "The
Diaper Test”
6. 1958 Dr. Robert Guthrie develops
"The Guthrie Test
1966 The Guthrie Test becomes standard
medical practice across the world
1992 Dr Savio Woo identifies the gene for the
mutated enzyme which causes PKU
1993 A Medical Research Council report
recommends that PKU patients should maintain
a low protein diet for life
7. Amino acids are the building blocks
for body proteins. 'Essential' amino
acids can only be obtained from the
food we eat as our body does not
normally produce them.
8. PHENYLALANINEPHENYLALANINE
Is essential amino acid
Normally degraded by way of the
tyrosine pathway
Phenylalanine and tyrosine are precursor
amino acids for important compounds
like:
11. In 'classic PKU', the enzyme that
breaks down phenylalanine
hydroxylase, is completely or nearly
completely deficient.
This enzyme normally converts
phenylalanine to another amino acid
tyrosine.
12. PKU is caused by a mutated gene for PAH
enzyme due to defect in the biosynthis of
cofactor tetrahydrobioptrin (BH4).
The PAH gene is located on chromosome
12 .
13. PAH deficiency causes a wide spectrum of
disorders including PKU and mild PKU or
hyperphenylalaninemia
19. These other disorders may be
caused by a partial deficiency of the
phenylalanine breakdown enzyme or
the lack of another enzyme
important to the processing of this
amino acid.
20. A normal blood phenylalanine level is
about 1 mg/dl.
In classic PKU, levels may range from
6 to 80mg/dl,
but are usually greater than 30mg/dl.
21. Prevalence :
Classic PKU and the other causes of
hyperphenylalaninemia affect about one
of every 10,000 to 20,000 Caucasian or
Oriental births. The incidence in
African Americans is far less.
22. These disorders are equally frequent in
males and females.
PKU prevalence is 1:12000 births
23. CAUSECAUSE
PKU and the other causes of
hyperphenylalaninemia are inherited
in a recessive fashion.
25. This means an affected person
inherited two traits for the disorder
(one from each parent). A person
with one trait for the disorder, is
called a 'carrier' for PKU. Carriers do
not have symptoms of the disorder.
28. About 50% of untreated infants have
early symptoms, such as
vomiting,
irritability
eczema-like rash,
and a musty odor to the urine and the
body.
29. Some may also have subtle signs of
nervous system function problems,
such as increased muscle tone, and
more active muscle tendon reflexes
32. Other commonly noted features in
untreated children include:
microcephaly (small head),
prominent cheek and upper jaw bones
with widely spaced teeth,
40. Usually, a few drops of blood are
obtained by a small prick on the heel,
placed on a card, and then sent for
measurement.
41. A positive blue-green color urine testing
indicates the presence of elevated levels
of phenylpyruvic acid
42. Plasma concentration of Phenyalaninemia
is higher than 20 mg / dl
For mild Phenylketonuria, plasma
phenylalanine concentration is between
2-10 mg /dl
46. If the screening test is abnormal,
other tests are needed to confirm or
exclude PKU. Newborn screening
allows early identification and early
implementation of treatment.
47. MEDICAL TREATMENTMEDICAL TREATMENT
Oral administration of tetrahydrobioptrin
( a cofactor in the oxidation of
phenylalanine) is a good potential for
PKU sufferers .
48. The goal of PKU treatment is to
maintain the blood level of
phenylalanine between 2 and 10 mg/dl.
Some phenylalanine is needed for
normal growth.
Nutritional
TREATMENT
49. This requires a diet that has some
phenylalanine but in much lower
amounts than normal.
50. Foods to avoidFoods to avoid
High protein foods, such as:
1- Meat
2-Fish
3- Poultry
4- Eggs
5- Cheese
6- Milk and products
7- Dried beans, and peas
51. 1- Measured amounts of cereals
2- Starches
3- Fruits
4-Vegetables
along with a milk substitute are usually
recommended.
Foods that can be given
55. In addition, lifestyle adjustments to
accommodate more frequent doctor
visits, and dietary restrictions may be
required and impact day to day activities.
56. In some clinics, a phenylalanine
'challenge' may be suggested to
evaluate whether or not the child
continues to require a low
phenylalanine diet.
57. This test identifies those few persons
with a transient or 'variant' form of
the disorder. However, most
authorities currently recommend
lifelong dietary restriction of
phenylalanine for individuals with
classic PKU, in order to promote
maximal development and cognitive
abilities.
58. Trying to reinstitute the PKU diet
after a period of 'relaxation' to a
regular diet, has been difficult for many
individuals.
59. Periodic phenylalanine blood level
measurement, and the guidance of a
nutritionist and other members of the
health care team, allow individuals and
families to work toward consistently
maintaining the blood level in the
desirable range.
60. Fever and illness can cause normal
body proteins to break down, the
liberation of the body's own amino
acids, and thus, a rise of the blood
phenylalanine level.
61. The physician and nutritionist can
suggest dietary changes to help
maintain levels in the desirable range
during illness.
62. These and other general issues are
important to understand and are
discussed in the accompanying topic
sheet for "Chronic Illness".
63. Untreated PKU can cause significant
brain problems including retarded
mental development. Current
screening for PKU in the newborn
period has made unrecognized PKU a
rare occurrence
64. With good dietary control, the
potential effects of PKU on
development are minimized. However,
recent studies indicate that loss of
dietary control in childhood can
interfere with cognitive development.
70. Because blood phenylalanine levels are
dependent on dietary control,
insufficient phenylalanine intake may
cause levels to be too low for growth
and body functions.
71. Low levels can cause mental and
physical sluggishness, loss of appetite,
anemia, rashes, and diarrhea.
72. The parent and/or nutritionist can
suggest appropriate and allowable
snack and mealtime foods outside the
home. Supporting appropriate dietary
habits, while minimizing attention to
dietary differences is important.
73. SUMMARYSUMMARY
Phenylketonuria is genetic disorder
characterized by an inability of the
body to utilize the essential amino
acid, phenylalanine.
phenylalanine hydroxylase, is
completely or nearly completely
deficient.
74. Without this enzyme, phenylalanine
and its breakdown chemicals from
other enzyme routes, accumulate in
the blood and body tissues
75. Symptoms range from vomiting to
difference in appearance
Diagnosis is done only by blood test
after birth
76. Treatment is done through taking
into consideration that high protein
foods, such as: meat, fish, poultry, eggs,
cheese, milk, dried beans, and peas
are avoided.