Scene 1: Michelle is saved by the starving bacteria

After this lesson, the student will be able to:1) explain recessive inheritance using phenylketonuria (PKU) as

an example;2) describe the Guthrie test for screening newborn babies for

PKU3) explain how PKU can be treated by a special diet and how this

could postpone the effects of PKU until the next generation4) discuss some of the economic issues associated with

screening for the treatment of genetic conditions5) explain why females with PKU need to be followed very closely

in their reproductive years to avoid the problems associated with maternal PKU.

Michelle’s Situation

Stacy and Paul Chance are referred to the genetics center because their newborn daughter, Michelle, had elevated phenylalanine levels as determined by newborn screening. The diagnosis of phenylketonuria (PKU) is made.

Mandatory PKU TestingThe couple wonders why their

child was tested. They have two other children, Alan (age 6) and Frank (12) who are apparently healthy, active, intelligent boys. The couple couldn't remember any special testing that either boy had at birth. State mandated newborn screening is explained to them. A description of PKU and its inheritance is provided, and dietary management is discussed.

PKU Testing: Guthrie Test• Mandatory statewide

testing around day 2 ($5/child)

• Bacteria grows on blood sample if excess phenylalanine is present

• Treatment begins immediately

• Why is $5/child more cost effective for the state then no testing at all?

What is PKU?

• PHENYLKETONURIA (PKU)– PAH gene on long arm of chromosome

12 is absent/reduced– Excess phenylalanine interferes with

brain development

• Autosomal recessive disorder1:10,000-15,000 births

• Effects: retardation, seizures, destructive, restlessness

Prognosis

• With treatment: Normal development

• With minimal treatment: Intellectual defects

• Without treatment: Retardation

Treatments• Low phenylalanine diet• Baby fed special

formula (~$10,000/year)

• Vegetables and low phenylalanine foods added later in development

• Regular blood samples taken and phenylalanine diet adjusted as needed

• Eventually, a normal diet can be obtained

Chemistry of PKU

• Normally, phenylalanine is converted into tyrosine and then into a protein

• The Problem: Enzyme phenylalanine hydroxylase is absent/reduced

• The result: Phenylalanine builds up in blood

Phenylalanine(amino acid)

Tyrosine(amino acid)

Melanin(protein)

Phenylalanine hydroxylase(enzyme)

Chances’ reactionIt’s not my fault Michelle is sick. I’m a successful business man. I don’t smoke. I jog 6 miles a day. I have a healthy diet.

Michelle’s problem must be due to a weakness of Stacy’s side of the family. I don’t have any “bad genes.”

Everyone carries 6-10 "unusual" recessive genes which cause no clinical problems in the carriers, but if two carriers of the same unusual recessive gene were to have children together, each child would have a 1 in 4 chance of inheriting the recessive condition for which the genes were responsible.

“but if two carriers of the same unusual recessive gene were to have children together, each child would have a

1 in 4 chance of inheriting the recessive condition”

HH (healthy)

Hh(healthy)

Hh(healthy)

hh

Stacy

Pau

l

Key

H = Healthy

h = PKU disease

H h

H

hhh

(PKU disease)

Genetic Counseling• Paul is relieved to know that being a carrier neither reflects negatively

on his manhood nor does it isolate him from his peers. He quickly turns the situation to his advantage and states,

• Stacy does not try to defend herself against Paul's earlier accusations but is relieved at his acceptance of the cause of Michelle's condition.

Well, if we're all carriers of some bad genes, I guess I'm better off than most of you. At least I know what one of my unusual genes is.

Genetic Counseling• The further complication of maternal PKU is mentioned. Paul and

Stacy are scheduled to meet with a nutritionist, and follow-up appointments for monitoring blood phenylalanine levels are made.

• Upon leaving, Stacy thanks the genetics staff and says,

• Little does she know...

Well I guess we won't be seeing you again for a long time.

Essay Topic #1

Assume that you are Stacy or Paul Chance. Describe in writing your feelings after your visit to the genetics center.

• Essay Format:

– Ink or typed (no pencil)

– Add title and date

– Minimal length = ¾ page

– If typed: 1” margins, 12-point times new roman font, double spaced.

– Complete essays (Introduction, body, conclusion)

– Spellcheck and proofread