PKU Screening - Part 2

Question 1

Outline the protocol for the follow up of Hyperphenylalaninaemia.

Answer 1

1) . Phe <200umol/L = Negative PKU test result and no further action.
2) . Phe >/=200-400umol/L = Carry out additional tests for other conditions - Gal, Tyr1, DHPR and biopterin screen on spot - if negative and baby is in hospital then discuss with clinician. If baby is in community then immediate repeat blood for ‘equivocal PKU test result’ via community midwife. If positive or repeat is positive then refer to duty biochemist to arrange immediate follow up.
3) . Phe >/= 400umol/L - confirm by TLC and carry out additional screens for other conditions - Gal, Tyr1, DHPR and biopterin screen on spot = refer to duty biochemist to arrange immediate follow up.

If the results remain equivocal then do full screen for other causes. If result is neg the it is clearly PKU neg. If remains between 200 and 400um/L then we would monitor it. If it is <400um/L then would monitor it and may start them on PKU dietary treatment.

Question 2

What diseases other than PKU can cause a raised phenylalanine level?

Answer 2

1) . Galactosaemia (Gal)
2) . Tyrosinaemia (Tyr1)
3) . DHPR abnormalities
4) . Biopterin abnormalities

Question 3

Describe PKU treatment.

Answer 3

• Dietary treatment as soon as possible (at latest by 21 days) for optimal outcome (Bickel in 1951 - protein restriction).
• The basis of the diet is low phenylalanine content supplemented with a protein substitute free of phenylalanine. L-amino acids or a protein hydrolysate free from phenylalanine, small and controlled amount of phenylalanine is required for normal growth and development. In neonate this is provided by breast or formula milk.
• In early infancy, plasma phenylalanine should be maintained between 120-360umol/L, the diet may be relaxed after 10 years of age but they are mostly advised to continue the diet for life.
• With early treatment and good dietary management development can be normal.
• Diet must be strictly controlled in pregnancy to avoid severe foetal damage.

Question 4

Describe how diet must be controlled if a patient with PKU wishes to become pregnant.

Answer 4

• Start them on a pre pregnancy diet for 3-4 months before conception. Phe levels may be running at 700 or 800um/L at that time so we start them on a very strict diet to keep their levels below 200um/L.
• The reason for this is because the placenta concentrates phe 2-4x and actively transports it across the placenta.
• If a foetus is exposed to high phe levels then they develop problems and may develop congenital abnormalities.
• For patients not on a regulated diet with PKU who have a baby 93% would have mental retardation, 73% Microcephaly, 40% Growth retardation, 12% Congenital anomalies.
• Recommendations are that maternal levels remain between 100 and 300umol/L from preconception and throughout pregnancy and diet must be closely monitored to avoid foetal damage from malnutrition.

Question 5

How do we regulate food in the case of babies and children with PKU?

Answer 5

• When the baby comes into the clinic the first day if the mother is breast feeding or bottle feeding then we will usually stop the breast milk for a couple of days. Breast milk contains phenylalanine because it contains protein.
• Would start the baby on a phenylalanine free diet that is supplemented with tyrosine and other essential amino acids.
• In the bottle milk their would be no phenylalanine but adequate tyrosine and other amino acids for the baby to grow normally.
• What we do know is that if the baby’s requirement is say 600mls a day then we will give the baby 600mls of milk split into feed and then after the baby has had the bottled milk the they could have breast milk. We then monitor the phenylalanine levels by heel prick. In the first week this would be done about 3 times per week and we adjust the amount of breast milk and the amount of nutrition according to the phenylalanine levels. At that stage we would like the phenylalanine levels to be below 300um/L.
• As they get older they stay on the bottle milk. They do need some phenylalanine. This would be aded into their body via exchanges. They may have breast milk or formula milk as exchanges to ensure that phenylalanine levels do not drop too low.
• When they start to ween we stop the formula milk, continue with the low phenylalanine milk and gradually add food in. If they were then to tae food they would have their phenylalanine-free food which they get on prescription. They then get amino acid supplements in either gel or liquid form - usually a drink 3 times a day.
• The lower they activity of the enzyme the fewer exchanges per day they will be allowed.
• During illness your body starts to break down endogenous muscle and will release phenylalanine into the circulation. This can also cause problems. During these times may supplement with extra calories.
• Also struggle sometimes with antibiotics as most have sweetener in. Ask GPs to prescribe high concentrations of antibiotics so we can give the sam doses in very low concentrations of the liquid.