Phenylketonuria (PKU) screening
Pre-activity assessment questions
• Note: The first two slides are intended for
first-time clicker users to become accustomed
to the devices.
Where do you live?
1.
2.
3.
4.
Sa
De
la
So
w
m
ar
ew
e
he
re
el
se
lis
bu
r
isb
Sa
l
th
an
er
yo
. ..
ur
y
ea
ar
on
Ot
h
m
ng
t
W
as
hi
or
e
ar
ea
17% 17% 17% 17% 17% 17%
Ba
lt i
Baltimore area
Washington area
Salisbury
Other than Salisbury
on the Eastern
Shore of MD
5. Delaware
6. Somewhere else
Have you studied genetics in your
school classroom?
25% 25% 25% 25%
1. Yes, a lot.
2. Yes, a little bit.
W
ha
td
o
No
,
yo
u
m
ea
n
by
g.
..
ve
ry
m
uc
h.
t.
bi
no
t
lit
t le
Ye
s,
a
Ye
s,
a
4. What do you mean
by genetics?!?!
lo
t.
3. No, not very much.
When a trait is inherited, what actually
passes from one generation to the
next? 25% 25% 25% 25%
1. Protein
2. DNA
3. RNA
4. Amino acids
Which words relate to DNA?
25% 25% 25% 25%
1. Deoxyribonucleic acid
2. Gene
De
o
e.
e
ab
ov
he
of
t
Ch
ro
m
os
om
Al
l
xy
r
ib
on
uc
le
ic
ac
id
4. All of the above.
Ge
ne
3. Chromosome
A trait is recessive if
t..
.
th
e
re
nt
of
if
bo
th
pa
es
co
pi
no
if
sh
ad
th
e
ng
co
di
DN
A
th
e
if
DN
A
t.
..
fo
ri
it .
..
fo
r
in
g
co
d
DN
A
th
e
a.
.
25% 25% 25% 25%
if
1. the DNA coding for it
must be inherited
from both parents.
2. the DNA coding for it
only needs to be
inherited from one
parent.
3. no copies of the DNA
are inherited from
the parents.
4. both parents had the
trait.
If both parents have a recessive
disease, what is the chance that their
child will have the same disease?
20% 20% 20% 20% 20%
1. 0%
2. 25%
en
ou
gh
in
fo
rm
at
io
n
..
10
0%
75
%
No
t
5. Not enough information
to answer the question.
25
%
4. 100%
0%
3. 75%
If neither parent has a recessive
disease, what is the chance that their
child will inherit a recessive disease?
1. 0%
20% 20% 20% 20% 20%
2. 25%
ou
gh
en
No
t
5. Not enough information given.
in
fo
rm
at
io
n.
..
10
0%
75
%
25
%
4. 100%
0%
3. 75%
How might you tell if someone has a
genetic disease?
25% 25% 25% 25%
1. Test his/her DNA.
2. Test his/her blood.
e.
s.
of
t
he
ab
ov
m
Al
l
di
se
as
e
kf
or
Lo
o
sy
m
pt
o
rb
lo
he
is/
st
h
Te
Te
st
hi
s/
4. All of the above.
od
.
he
rD
NA
.
3. Look for disease symptoms.
A genetic disease that all newborn
babies get tested for is
1. HIV
25% 25% 25% 25%
2. Phenylketonuria
s
be
te
Di
a
ce
r
Ca
n
ia
to
nu
r
ke
ny
l
Ph
e
4. Diabetes
HI
V
3. Cancer
All people with PKU are hyperactive
and have seizures and rashes.
50%
1. True
50%
se
Fa
l
Tr
ue
2. False
People with PKU need to avoid a
high protein diet because
.
bo
ve
ea
th
of
to
o
av
e
yh
th
e
No
ne
m
uc
h
ca
u
ts
di
e
te
in
pr
o
h
ph
...
se
.. .
a.
.
it
o
ds
t
bi
n
hi
g
th
ei
rD
NA
1. their DNA binds to it and
makes them sick.
2. high protein diets cause
heart disease.
3. they have too much
phenylalanine in their
blood.
4. None of the above.
25% 25% 25% 25%
Phenylalanine is a(n)
25%
1. gene
25%
25%
25%
2. protein
3. amino acid
as
e
di
se
am
in
o
ac
id
n
te
i
pr
o
ge
ne
4. disease
Simulated Guthrie screen for PKU
(Phenylketonuria)
Newborn screening for genetic disease
Newborn genetic testing
• Chemical analysis of blood samples
• Detects lack or excess of important
metabolites and hormones
• Detects red blood cell abnormalities
• Ideal if fast and inexpensive
• Ideal to identify and treat diseases as soon as
possible
• Important knowledge for future generations
• Specific tests vary somewhat from state to
state
Phenylketonuria (PKU) inheritance
• Inherited, recessive disease
• About 1 in 15,000 babies born in the United
States inherit PKU.
• People with PKU (phenylketonurics) can’t
break down phenylalanine, a common amino
acid
• All newborns in United
States are screened for
PKU
Neither parent
has the disease,
but children
can inherit it.
Phenylketonuria (PKU)
• Excess phenylalanine, a common amino acid
• Phenylalanine accumulates, causing rashes,
seizures, hyperactivity, and mental
retardation, if untreated.
• No cure.
• Disease is managed by avoiding foods high
in proteins containing phenylalanine.
Phenylalanine
(Phe)
Newborns are screened for PKU
• All US babies are screened for PKU by
heel-prick test.
• Blood tested for excess phenylalanine.
• Blood placed on agar plate with bacteria
that need phenylalanine to grow.
• Healthy babies’ blood doesn’t have extra
phenylalanine, so bacteria can’t grow
• Babies with PKU have extra
phenylalanine, so bacteria grow
Guthrie test for PKU
Bacterial plate with newborn blood samples
Positive blood test results: bacterial
halo = PKU
Negative controls: no bacterial
growth
Positive controls : increasing
phenylalanine concentrations give
bacterial halos
Negative blood test results: no
bacterial growth = healthy babies
http://www.childrenshospital.org/cfapps/research/data_admin/Site2940/mainpageS2940P4sublevel15.html
Simulated Guthrie screen for PKU
• Place filter with “newborn blood sample” onto
agar plate. Wait 10- 15 minutes.
• Include positive and negative control samples.
– What is used for these controls?
• Look for agar plate color to change to indicate
positive results.
• Remove filters if necessary.
Positive control
“Blood” samples
+
-
Negative
control
Amino acids make proteins
• Phenylalanine (Phe) is an amino
acid found in almost all proteins.
• 20 amino acids make up all the
proteins found in living things.
• Proteins are chains of linked amino
acids that give cells shape or act
like machines to do work in cells.
Proteins cause most traits in living things
Proteins are linked amino acids that give cells
shape or act like machines to do work in a cell.
Protein sequences are determined by DNA.
Keratin protein makes hair
GFP makes
green
fluorescent
protein
Animal muscles are
made of protein.
Enzyme makes
purple
pigment
PKU is caused by DNA mutations
• People with PKU have inherited mutations in the
gene coding for a protein that regulates
phenylalanine levels.
• Phenylketonurics have too much
phenylalanine in their blood.
• Excess phenylalanine causes disease
symptoms, like mental retardation.
• Keeping phenylalanine blood levels low
allows healthy life.
PKU Diet:
low protein = low phenylalanine
• Lofenalac special infant formula, low in
phenylalanine
• Phenylalanine-free nutrient mixes for adults.
• Little to no milk, cheese, eggs, meat, fish, beans,
nuts, or other high protein foods.
• Fruits and vegetables are
the most safe foods.
• Certain “diet” or “light”
foods must be avoided
completely.
Sickenly sweet Aspartame
• Aspartame = artificial sweetener made from
amino acids phenylalanine and aspartic acid
• Found in “diet”, “light”, and “sugar-free” foods
• Highly toxic to people with PKU
Do the blood samples you are testing
come from babies with PKU?
Post-activity assessment questions
When a trait is inherited, what actually
passes from one generation to the next?
25%
25%
25%
25%
1. Protein
2. DNA
3. RNA
Am
in
o
ac
id
s
RN
A
DN
A
Pr
ot
ei
n
4. Amino acids
Which words relate to DNA?
1. Deoxyribonucleic acid
25% 25% 25% 25%
2. Gene
e.
e
ab
ov
he
of
t
Ch
ro
m
os
om
Al
l
De
ox
yr
ib
on
uc
le
ic
ac
id
4. All of the above.
Ge
ne
3. Chromosome
A trait is recessive if
t..
.
th
e
re
nt
of
if
bo
th
pa
es
co
pi
no
if
sh
ad
th
e
ng
co
di
DN
A
th
e
if
DN
A
t.
..
fo
ri
it .
..
fo
r
in
g
co
d
DN
A
th
e
a.
.
25% 25% 25% 25%
if
1. the DNA coding for it
must be inherited
from each parent.
2. the DNA coding for it
only needs to be
inherited from one
parent.
3. no copies of the DNA
are inherited from
the parents.
4. both parents had the
trait.
If both parents have a recessive
disease, what is the chance that their
child will have the same disease?
1. 0%
20% 20% 20% 20% 20%
2. 25%
ou
gh
en
No
t
5. Not enough information
given.
in
fo
rm
at
io
n.
..
10
0%
75
%
25
%
4. 100%
0%
3. 75%
If neither parent has a recessive
disease, what is the chance that their
child will inherit a recessive disease?
1. 0%
20% 20% 20% 20% 20%
2. 25%
en
ou
gh
in
fo
rm
at
io
n.
..
10
0%
75
%
No
t
5. Not enough information given.
25
%
4. 100%
0%
3. 75%
How might you tell if someone has a
genetic disease?
25% 25% 25% 25%
1. Test his/her DNA.
2. Test his/her blood.
e.
ab
ov
he
of
t
Al
l
di
se
as
e
sy
m
pt
o
m
s.
od
.
rb
lo
he
Lo
o
kf
or
Te
st
h
is/
is/
Te
st
h
4. All of the above.
he
rD
NA
.
3. Look for disease symptoms.
A genetic disease that all newborn
babies get tested for is
1. HIV
20% 20%
20% 20% 20%
2. Phenylketonuria
3. Cancer
Ph
e
ia
ny
l
ke
to
nu
r
ce
r
Ca
n
s
be
te
Di
a
HI
V
4. Diabetes
All people with PKU are hyperactive and
have seizures and rashes.
1. True
50%
50%
se
Fa
l
Tr
ue
2. False
People with PKU need to avoid a high
protein diet because
e.
ab
ov
he
of
t
m
to
o
av
e
yh
th
e
Al
l
uc
h
ca
u
ts
di
e
n
te
i
pr
o
h
ph
...
se
.. .
a.
.
it
o
ds
t
bi
n
hi
g
th
ei
rD
NA
1. their DNA binds to it
and makes them sick.
2. they have too much
phenylalanine in their
blood.
3. high protein diets
cause heart disease.
4. All of the above.
25% 25% 25% 25%
Phenylalanine is a(n)
1. gene
25%
25%
25%
25%
2. protein
3. amino acid
as
e
di
se
am
in
o
ac
id
n
te
i
pr
o
ge
ne
4. disease
1. Write down one interesting thing that you
learned in this session.
2. Write down one question that you have or
something that confused you in this session.
Additional slides
More multiple choice ideas
• What is the difference between phenylalanine
and PKU ? Phe is a building block for
proteins, while PKU is a disease (and
variations)
• What is the relationship between a protein
and an amino acid? Amino acids are the
building blocks for proteins (and variations).
Proteins are coded by DNA
• DNA sequence determines amino
acid sequence in proteins.
• Amino acid sequence determines
protein structure and function.
• Changes, or mutations, in DNA
cause changes in protein’s amino
acid sequence.
• Changes in protein structure cause
changes in protein function.
• Changes in protein function cause
altered traits, sometimes disease.
trait
Proteins cause most traits in living things
Proteins are linked amino acids that give cells
shape or act like machines to do work in a cell.
Proteins are encoded by DNA.
Keratin makes hair
GFP makes
green
fluorescent
protein
Enzyme makes
purple
pigment
Phenylalanine
hydroxylase enzyme
breaks down
phenylalanine
PKU is caused by DNA mutations
• People who inherit PKU have inherited mutations in
the gene coding for a digestive protein (enzyme).
• Phenylalanine hydroxylase enzyme breaks down
phenylalanine.
• Phenylketonurics don’t have working
phenylalanine hydroxylase, so they can’t
break down phenylalanine.
Phenylalanine
• Phenylalanine accumulation causes
hydroxylase
disease symptoms, like mental retardation. enzyme breaks
down
phenylalanine