Integrated PBL: Phenylketonuria (PKU)

Question 1

What is phenylalanine?

Answer 1

Crystalline, water-soluble, essential amino acid necessary to the nutrition of humans and most animals, obtained chiefly from egg white or skimmed milk

Question 2

What is a teratogenic substance?

Answer 2

A drug or other substance capable of interfering with the development of a foetus

Question 3

What is microcephaly?

Answer 3

Abnormal smallness of the head, a congenital condition associated with incomplete brain development

Question 4

What is anaemia?

Answer 4

Condition where there is a deficiency of red cells or of haemoglobin in the blood

Question 5

What is folate?

Answer 5

One of the B vitamins that is a key factor in the synthesis of nucleic acids (RNA and DNA)

Question 6

What is the cause of PKU?

Answer 6

Caused by a genetic mutation to human phenylalanine hydroxylase (PAH) gene leading to the body not producing a functioning PAH enzyme

Question 7

When do symptoms of PKU occur?

Answer 7

If untreated; at birth most babies with PKU appear normal and symptoms only develop because of complications that arise if the condition isn’t treated properly

Question 8

When should treatment of PKU be initiated?

Answer 8

Within the first 3 weeks of life to minimise the chance of them experiencing severe learning difficulties associated with the condition

Question 9

What are the most widely reported conditions in adults with treated PKU?

Answer 9

Depression, anxiety disorders, phobias (particularly agoraphobia) and low self-esteem

Question 10

What are the symptoms of untreated PKU?

Answer 10

Severe learning disability, behavioural difficulties,

Question 11

Why may those with untreated PKU have fairer skin, hair and eyes?

Answer 11

Phenylalanine is involved in the body’s production of melanin, the pigment responsible for skin and hair colour

Question 12

What is PKU?

Answer 12

Disorder where there are insufficient PAH enzyme so any excess phenylalanine can’t be broken down, and therefore phenylalanine can build up in the blood and brain to toxic levels, affecting brain development and function

Question 13

How is PKU diagnosed?

Answer 13

Heel prick test in the first 7 days of life, testing for phenylalanine levels; if they are higher than normal a diagnosis of PKU is given (if greater than 3mg/dL) and dietary treatment is begun

Question 14

How is PKU treated?

Answer 14

With a low-protein diet and regular dietary supplements containing essential nutrients and amino acids absent from the diet; taken 3 to 4 times a day

Question 15

What are ‘green foods’ in a low-protein diet for treating PKU?

Answer 15

Foods that are safe to eat because they contain low levels of protein, though they shouldn’t be eaten in excess. These include most fresh fruit, most vegetables, low-fat and low-protein butter and margarine

Question 16

What are ‘amber foods’ in a low-protein diet for treating PKU?

Answer 16

Foods that contain moderate levels of protein and must be carefully weighed and eaten in different quantities according to the blood phenylalanine level. These include potatoes, cereals, baked beans, milk and rice

Question 17

What are ‘red foods’ in a low-protein diet for treating PKU?

Answer 17

High-protein foods that should never be eaten under any circumstances. These include all types of meat, fish, eggs, cheese, nuts, flour-based foods and quorn/tofu

Question 18

Why can’t individuals with PKU consume aspartame/artificial sweetener?

Answer 18

Aspartame is converted to phenylalanine in the body

Question 19

Why do excessive phenylalanine levels cause microcephaly?

Answer 19

Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the blood–brain barrier (BBB) via the large neutral amino acid transporter (LNAAT). If phenylalanine is in excess in the blood, it will saturate the transporter. Excessive levels of phenylalanine tend to decrease the levels of other LNAAs in the brain. As these amino acids are necessary for protein and neurotransmitter synthesis, Phe buildup hinders the development of the brain, causing intellectual disability

Question 20

Why is tyrosine a conditionally essential amino acid in PKU?

Answer 20

PAH converts the phenylalanine to other essential compounds in the body, in particular tyrosine. Tyrosine is a conditionally essential Amino acid for PKU patients because without PAH it cannot be produced in the body through the breakdown of phenylalanine. Tyrosine is necessary for the production of neurotransmitters like epinephrine, norepinephrine, and dopamine

Question 21

Describe the epidemiology of PKU

Answer 21

Affects 1:10,000 babies born in the UK and both sexes are affected equally

Question 22

Why may the pregnant woman with PKU have symptoms of tiredness, paleness and weight loss?

Answer 22

Likely to have stopped taking nutritional supplements, and due to the lack of iron present in the low-protein diet, are likely to have developed iron-defiency anaemia and have begun to lose weight due to lack of essential vitamins and minerals

Question 23

How may PKU be inherited?

Answer 23

It’s an autosomal recessive condition; so both partners would have to have PKU or both be a carrier, or a carrier and someone with PKU.

Question 24

Describe the symptoms of an ACL tear

Answer 24

Acute knee pain and pain when climbing the stairs

Question 25

Describe the treatment of an ACL tear

Answer 25

Rest the knee, elevate the knee, wear knee brace, take NSAIDs to help with pain and swelling, practice stretching and strengthening exercises to reduce knee swelling OR surgery may be required using autograft from tendons elsewhere or allograft from a cadaver

Question 26

What do the individual’s low haemoglobin levels indicate?

Answer 26

Indicative of anaemia, but doesn’t tell you which kind

Question 27

What do the individual’s low haematrocrit levels indicate?

Answer 27

Small amount of red blood cells in the blood –> anaemia

Question 28

What does the individual’s low MCV indicate?

Answer 28

The red blood cells are not enlarged, and therefore this doesn’t indicate folate or B12 deficiency anaemia, so it is likely to be as a result of iron-deficiency

Question 29

What do the individual’s low ferritin levels indicate?

Answer 29

Ferritin is a protein that stores iron, therefore low levels directly suggest that there is a low level of iron in the blood as there isn’t enough to be stored and therefore this is likely due to not taking the appropriate nutritional supplementation (as diet doesn’t have enough iron as it’s low-protein, therefore no red meat etc)

Question 30

What do the individual’s normal folate levels indicate?

Answer 30

Levels are normal but are on slightly the low side which may explain why she is extremely tired and confused as these are symptoms that lower levels of folate can cause

Question 31

What do the individual’s low phenylalanine levels indicate?

Answer 31

Indicates she is taking the low-protein diet to the extreme and not consuming the right amount of protein

Question 32

Describe the role of the PKU treatment centre

Answer 32

During pregnancy you’re asked to provide blood samples 3 times a week and are in frequent contact with a dietician