PKU

Question 1

Definition of Phenylketonuria

Answer 1

PKU is an inherited disorder that causes the amino acid phenylalanine to build up the body

Question 2

Which gene is the culprit of PKU

Answer 2

phenylalanine hydroxylase (PAH) gene

Question 3

what does the PAH gene normally do

Answer 3

creates the enzyme needed to break down phenylalanine

Question 4

What happens without the enzyme (PAH)?

Answer 4

phe builds up in the blood and brain, leading to brain damage

Question 5

mechanism of the PAH enzyme

Answer 5

catalysing reaction of Phe to Tyr

Question 6

What are the different types of PKU in increasing severity

Answer 6

1. Hyperphenylalaninemia
2. Mild PKU
3. Moderate or variant PKU
4. Classic PKU

Question 7

What are the most common symptoms of the milder forms of PKU?

Answer 7

Irritability, Intellectual disability, problems with memory

Question 8

what are the symptoms of Classic PKU

Answer 8

Seizures, microcephaly, behavioral problems, musty/mouse-like buildup, lighter skin & hair, eczema

Question 9

Who first documented PKU in 1934 and how?

Answer 9

Ivar Asbörn Følling, by testing urine samples for ketones

Question 10

What were the results of Folling’s ketone test?

Answer 10

The sample turned green instead of the normal red-brown or purple due to phenylpyruvic acid

Question 11

Geoge Jervis (1947) localized the PKUmetabolic error as

Answer 11

an inability to oxidize phenylalanine hydroxylase in the liver

Question 12

Horst Bickel, John Gerrad, and Evelyn Hickman created _______

Answer 12

a diet low in Phe which improved the conditions of those with PKU

Question 13

In 1958, Robert Guthrie created

Answer 13

a simple blood test to test children for PKU after birth

Question 14

prevalence of PKU in the US

Answer 14

1 in 15,000

Question 15

Which country has the highest incidence rate of PKU

Answer 15

Turkey has 1 in 4000

Question 16

The PKU incidence rate is higher in population of __________ and lower in __________

Answer 16

Caucasian and Native American

African-American, Hispanic, and Asian individuals

Question 17

properties of PAH gene

Answer 17

located on chromosome 12, ~100 kb, 13 exons and 12 introns, has many variants

Question 18

where is PAH mostly expressed

Answer 18

in the liver and kidneys

Question 19

PKU inheritance pattern

Answer 19

autosomal recessive

Question 20

do Vinay’s parents have PKU

Answer 20

no, they are both carriers

Question 21

How is PKU diagnosed

Answer 21

1. chorionic villia sampling or amniocentesis (invasive)
2. cell-free fetal DNA analysis (non-invansive)

Question 22

Is there a cure for PKU?

Answer 22

No. symptoms are controlled

Question 23

How are manifestations of PKU symptoms maintained?

Answer 23

low-protein diet, PKU medication, routine monitoring of blood Phe levels

Question 24

Which foods do those with PKU avoid

Answer 24

Meat, eggs, dairy, beans, peas nuts, aspartame

Question 25

What is Palynziq (Pegvaliase)?

Answer 25

PKU treatment - an enzyme that catabolize Phe to ammonia and trans-cinnamic acid -> decreases overall Phe levels

Question 26

what is Kuvan (sapropterin dihydrochloride)?

Answer 26

PKU treatment - a synthetic version of BH4, a cofactor for the PAH enzyme -> promotes PAH activity

Question 27

What are Large Neutral AA’s?

Answer 27

PKU treatment - competitive with Phe in transportation past the BBB -> decreases Phe buildup in the brain