PBL5

Question 1

Phenylketonuria

Answer 1

this is a metabolic condition and a rare genetic condiciton that causes the amino acid phenylalanine to build up in the body and in the brain which can cause many complications

Question 2

teratogenic

Answer 2

this is an agent that can half the pregnancy or produce a congenital malformation, they can come in the form of drugs, it can cause things such as

Question 3

microcephaly

Answer 3

this is abdominal smallness of the head, this is caused and associated with incomplete brain development

Question 4

congenital heart defects

Answer 4

– these are problems with the heart that are caused by underdevelopment and are what people are born with, for example a hole in the heart caused by when the foramen ovalis does not close up between the right and left atria

Question 5

mental retardation

Answer 5

this is the condition of having an IQ that is measured as below 70-75 and significant delays or lacks in at least two areas of adaptive skills

Question 6

describe phenylalanine

Answer 6

• Aromatic and essential amino acid
• It is both glucogenic and ketogenic
• It is converted to tyrosine

Question 7

what are the sings and symptoms of phenylalanine

Answer 7

• CNS abnormalities – behaviour difficulties, jerking movement, tremors and epilepsy
• Reduced melanin – fairer skin, fair hair, blue eyes – phenylalanine is involved in making melanin therefore when it is inhibited there is a reduced amount of melanin
• Ketones in the blood- musty odous
• Eczema and recurrent vomiting

Question 8

what is the treatment of PKU

Answer 8

• Diet – via a low protein diet, specially desiged products such as flour rice and pasta
• Drugs – sapropternin BH4 treatment of PKU this increases the tolerance to phenylalanine
• PKU formula – drink with a special formula mixed with small amounts of breast milk to ensure that child gets enough phenylalainine for normal developlnet

Question 9

explain the table of results

Answer 9

• Mean corpuscular volume is lower than 80 this means that she has microcytic anaemia
• This is caused by the reduced ferritin which means that she is not taking in iron
• She also has a reduced phenyalalnine
• Haemoglobin is reduced and haemotcrit is reduced due to a lower amount of red blood cells this is due to the iron deficiency

Question 10

describe the genetics of PKU

Answer 10

• Mutation of phenylalanine hydroylase on chromosome 12 q arm 22 to q arm 24.1
• missense tyrtophan instead of arginine
• It is an autosomal recessive conditions
• Some rare forms can be due to insufficient tetrahydrobiopterin - non classical PKU, this is a cofactor for PAH, deficiency due to defect in biosynthesis or recycling
• Levels of dopamine can be used to distinguish between the two types of PKU. BH4 is required to convert Tyr to L-DOPA via tyrosine hydroxylase. Low levels of dopamine can increase levels of prolactin. In classic PKU would see this as normal

Question 11

describe normal phenylamine metabolised in the body

Answer 11

Normally
In the body
Phenylalanine is made from dietary protein
It is converted to phenylalanine
Then phenylalanine is converted to tyrosine by phenylalanine hydroxylase (this is present in the liver), this reaction is irreversible and requires folate B9
Then tyrosine is converted to DOPA
DOPA can then either be converted to DOPA quinone or dopamine
DOPA quinone is melanin (this is a pigament of skin, hair and eye) and dopamine is a catecholamine

Question 12

describe how PKU effects phenylalanine metabolism

Answer 12

• Phenylalanine hydroxylase is inhibited by BH4 (tetrahydrobiopterin)
• This means that phenylalanine is converted to phenylpyruvate and this breaks into phenylacetate and phenylacetate
• This casues the build up of phenylalaine
• Develop toxic levels of phenylalanine in the body and a high ratio of phenylalanine to tyrosine and this is associated with impairment of the production of neurotransmitters
• If untreated it can lead to a learning disability

Question 13

how is PKU diagnosed

Answer 13

• At 5 days old babies are offered new born blood spot screening by pricking at the back of the heel
• Means that they can change there diet and avoid learning difficulites
• Can have a genetic screen to confirm mutation that gives PKU phenotype
• Measure the ratio of phenylalanine to tyrosine this is normally elevated in PKU
• Look at levels of phenylketones

Question 14

what is tyrosine a precursor for

Answer 14

Protective role acting to reduce the breakdown of
elastin by elastase in lung tissue

Deficiency (=similar effect to smoking): pulmonary
emphysema

Question 15

what is the consequence of lack tyrosine

Answer 15

• affects myelination and white matter tracts this can lead to neurological disorders, severe intellectual disability, microcephaly and mood disorders

Question 16

what are the blood spot screening programme

Answer 16

• medium chain acyl CoA dehydrogenase deficiency
• maple syrup urine disease
• isolvaleric acideameia
• homocystinuria
• glutamic acuduria type 1

Question 17

how is PKU control in pregnancy

Answer 17

Diet → control intake of protein, brain damage in
adults vs foetus

Continuous monitoring of blood levels and foetus
throughout preconception and conception –
checked 2-3 times per week

Full amino acid profile, vitamins and FBC each
trimester

MDT

Antenatal and delivery care same as women
without PKU, few more precautions

Preconception Counselling

Question 18

what does genetic counselling do

Answer 18

Provides information for families wanting to know
the risk of a condition to their child or future child.

Gives advice on what parents can do about living
with the child.

How to talk to family members who may be
carriers.

Provide information on support groups and leaflets.

Question 19

what is the abbreviation for the cofactor biopterin

Answer 19

BH4