PKU must be detected quickly so that treatment can be started within the first 20 days of life. When performing the diagnosis it can also be useful to calculate the amount of protein ingested and a measure of plasma amino acids. Errors in biopterin metabolism should also be ruled out. If there is a defect in biopterin metabolism the treatment will be different as a low phenylalainine diet is not successful. This is because two other enzymes are deficient, tyrosine hydroxylase and tryptophan hydroxylase. These are co-factors required for the normal activity of phenylalanine hydroxylase which functions normally in this condition. They help produce monoamine transmitters; adrenaline, noradrenaline and dopa. If these two enzymes are not replaced during treatment then neurological defects will result due to damage of the developing CNS. If the enzymes themselves are not replaced then the neurotransmitters should be.
There is currently no means of detecting carriers in the population.
Treatment for classic PKU is usually in the form of a diet low in phenylalanine. Babies should be started on this diet if their blood phenylalanine levels are greater than 600 micro moles/litre whether or not they have a low tyrosine level. They should also commence treatment if concentrations are between 400 and 600 micro moles/litre for their first few days if life.
The diet should contain 100 to 200 mg/kg/day of tyrosine and total protein should be at 2g/kg/day which should be eaten relatively evenly throughout the day. It should be very low in phenylalanine and the level of this in the diet needs to be adjusted depending on blood concentrations. It cannot be left out of the diet completely because it is an essential amino acid. The diet is to ensure that blood phenylalanine concentration do not exceed 360 micro moles/litre or fall below 120 micro moles/litre. These need to be measured in the morning when readings will be at their highest.
Phenylalanine concentration can reach 480 micro moles/litre in school children without causing any neurological damage. This is because as age increases it becomes more difficult to control blood levels. However, it should not be allowed to exceed 700 micro moles/litre.
If a women falls pregnant and she has not been on this strict diet then she should be offered a termination if her blood phenylalanine is greater than 900 micro moles/litre. The chances of her child having mental retardation at this concentration is virtually 100%. There is also a high risk of congenital heart defects. It is particularly important that this diet is adhered to before conception and right through pregnancy because the placenta exhibits a positive amino acid gradient. This means that her child will be exposed to an even higher phenylalanine concentration than her. If concentrations are above 700 micro moles/litre the woman should have full investigations because there is also a great risk of her child having abnormalities. She may also need to be offered a termination.
The better this diet is adjusted and adhered to the lesser the chance of complications. This method of treatment is usually very effective, however, it requires life long commitment to a restricted diet which can be artificial in flavour. This can also have implications for family and friends as their diets and lifestyles may be affected.
Finally, treatment via gene therapy is not yet possible because DNA/protein complexes being tested are destroyed by the immune system. The enzyme itself has been made but there is no effective method of administering it (Eisensmith et al, 1996).
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