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?

Baltimore are

a

Wash

ington are

a

Salis

bury

Oth

er than Salis

bury o...

Delaware

Somewhere

else

17% 17% 17%17%17%17%1. Baltimore area2. Washington area3. Salisbury4. Other than Salisbury

on the Eastern Shore of MD

5. Delaware6. Somewhere else

Have you studied genetics in your school classroom?

Yes, a lo

t.

Yes, a litt

le bit.

No, n

ot very m

uch.

What d

o you m

ean by g...

25% 25%25%25%

1. Yes, a lot.

2. Yes, a little bit.

3. No, not very much.

4. What do you mean by genetics?!?!

When a trait is inherited, what actually passes from one generation to the

next?

1. Protein

2. DNA

3. RNA

4. Amino acids

Which words relate to DNA?

Deoxy

ribonucle

ic acid

G

ene

Chromoso

me

All of t

he above.

25% 25%25%25%

1. Deoxyribonucleic acid

2. Gene

3. Chromosome

4. All of the above.

A trait is recessive if

if th

e DNA co

ding for it

...

if th

e DNA co

ding for i

t ...

if no co

pies of t

he DNA a..

if both

parents had th

e t...

25% 25%25%25%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?

0%25%

75%100%

Not e

nough in

form

ation ..

20% 20% 20%20%20%

1. 0%

2. 25%

3. 75%

4. 100%

5. Not enough information to answer the question.

If neither parent has a recessive disease, what is the chance that their child will inherit a recessive disease?

0%25%

75%100%

Not e

nough in

form

ation...

20% 20% 20%20%20%

1. 0%

2. 25%

3. 75%

4. 100%

5. Not enough information given.

How might you tell if someone has a genetic disease?

Test

his/her D

NA.

Test his/

her blood.

Look f

or dise

ase sy

mptoms.

All of t

he above.

25% 25%25%25%

1. Test his/her DNA.

2. Test his/her blood.

3. Look for disease symptoms.

4. All of the above.

A genetic disease that all newborn babies get tested for is

HIV

Phenylketonuria

Cancer

Diabete

s

25% 25%25%25%

1. HIV

2. Phenylketonuria

3. Cancer

4. Diabetes

All people with PKU are hyperactive and have seizures and rashes.

Tru

e

False

50%50%1. True

2. False

People with PKU need to avoid a high protein diet because

their

DNA binds to it

a..

high protein diets

cause

...

they h

ave to

o much

ph...

None of t

he above.

25% 25%25%25%

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.

Phenylalanine is a(n)

gene

protein

amino acid

diseas

e

25% 25%25%25%

1. gene

2. protein

3. amino acid

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 extraphenylalanine, so bacteria grow

Guthrie test for PKU

Bacterial plate with newborn blood samples

Negative controls: no bacterial growth

Positive blood test results: bacterial halo = PKU

Negative blood test results: no bacterial growth = healthy babies

Positive controls : increasing phenylalanine concentrations give bacterial halos

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.

“Blood” samples

Positive controlNegative 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 thingsProteins 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

Enzyme makes purple

pigment

GFP makes green

fluorescent protein

Animal muscles are made of protein.

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?

1. Protein

2. DNA

3. RNA

4. Amino acids P

rote

in D

NA RNA

Amino acids

25% 25%25%25%

Which words relate to DNA?

Deoxyri

bonucleic

acid G

ene

Chromoso

me

All of t

he above.

25% 25%25%25%1. Deoxyribonucleic acid

2. Gene

3. Chromosome

4. All of the above.

A trait is recessive if

if th

e DNA co

ding for it

...

if th

e DNA co

ding for i

t ...

if no co

pies of t

he DNA a..

if both

parents had th

e t...

25% 25%25%25%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?

0%25%

75%100%

Not e

nough in

form

ation...

20% 20% 20%20%20%

1. 0%

2. 25%

3. 75%

4. 100%

5. Not enough information given.

If neither parent has a recessive disease, what is the chance that their child will inherit a recessive disease?

0%25%

75%100%

Not e

nough in

form

ation...

20% 20% 20%20%20%

1. 0%

2. 25%

3. 75%

4. 100%

5. Not enough information given.

How might you tell if someone has a genetic disease?

Test his/

her DNA.

Test his/

her blood.

Look f

or dise

ase sy

mptoms.

All of t

he above.

25% 25%25%25%

1. Test his/her DNA.

2. Test his/her blood.

3. Look for disease symptoms.

4. All of the above.

A genetic disease that all newborn babies get tested for is

HIV

Diabete

s

Cancer

Phenylketonuria

20% 20% 20%20%20%1. HIV

2. Phenylketonuria

3. Cancer

4. Diabetes

All people with PKU are hyperactive and have seizures and rashes.

1. True

2. False

Tru

e

False

50%50%

People with PKU need to avoid a high protein diet because

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. th

eir DNA binds t

o it a..

high protein diets

cause

...

they h

ave to

o much

ph...

All of t

he above.

25% 25%25%25%

Phenylalanine is a(n)

gene

protein

amino acid

diseas

e

25% 25%25%25%

1. gene

2. protein

3. amino acid

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 thingsProteins 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

Enzyme makes purple

pigment

Phenylalanine hydroxylase enzyme

breaks down phenylalanine

GFP makes green

fluorescent protein

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.

Phenylalanine hydroxylase

enzyme breaks down

phenylalanine

• Phenylketonurics don’t have working phenylalanine hydroxylase, so they can’t break down phenylalanine.

• Phenylalanine accumulation causes disease symptoms, like mental retardation.