Collated and co-written by Rachael Sharman, parent (3-MCC) and Vice President MDDA.
Co-written and edited by Dr Jim McGill, Director Metabolic Medicine, Royal Children's Hospital, Brisbane, Queensland, Australia.
Phenylketonuria (PKU) is an inborn error of protein metabolism resulting from a deficiency of the enzyme, phenylalanine hydroxylase, that is needed to break down one amino acid in protein - phenylalanine (phe). Phe is normally converted to tyrosine, which in turn is converted to one of the neurotransmitters (chemicals which carry messages between brain cells). As individuals with PKU are unable to properly breakdown Phe into tyrosine this results in higher Phe levels and lower Tyrosine levels in the blood and brain.
Untreated, the effects of this disorder are devastating. The build up of phe in the brain, along with diminished levels of tyrosine and other neurotransmitters, cause irrepairable neurological damage. In a population of untreated individuals, just under half would have no speech and little comprehension and many more would be unable to live independently. Some would have a better prognosis (although still brain damaged) due to rare individual variations/mutation, possibly involving higher tyrosine levels in the brain.
Since the 1960's, PKU babies have been identified via the heel prick test and treated within the first few days of life. The prognosis since the introduction of diagnosis via the heel prick test continues to improve. Adults who were treated from the time they were infants in the 1960's have normal intelligence which, on average, tends to be at the lower end of the normal range. PKU children born today can expect an IQ that is not significantly different than their peers so long as diet, supplements and treatment is maintained. Although opinions vary (along with individual presentation of the disorder), current thought is that diet should be maintained for life.
As Phe is found in all food-based protein, the diet is a low protein diet. Protein intake ranges from 5g - 15g protein per day on average. A slice of bread contains 3g of protein, a banana 1g, a small serve of meat 40g. The diet prescribed is essentially vegan and includes a range of highly specialised manufactured products (eg milks, breads,pastas). Most Australian users calculate exact phe content, which is typically measured in "units". A unit is generally one third of a gram of protein, but this is not always the case as some food proteins may be proportionally higher or lower in phe than others. Most families use an Australasian manual (the green book) to calculate phe content. All food must be weighed carefully using specialised scales so exact calculations of phe content can be made. Even something as innocuous as a cherry tomato contains half a unit, and this must be calculated into daily allowance. Non-phe protein supplements eg XP Maxamaid, XP Maximum, Phenex 2 and PKU gel are also essential to maintain normal growth and development.
The main issues for affected individuals and their families revolve around maintaining diet. The foods are expensive and do not constitute a terribly appealing diet. Monitoring of phe levels is via blood test, and is not always an accurate indication of how the brain is being affected. The "allowable" protein intake is unlikely to increase significantly as people age, meaning the diet becomes harder to comply with as growth and ageing occur. Adults who go off diet are often reported to be more difficult to live with (grumpier, shorter temper etc). Some have a reduction in their ability to think clearly and this may cause a reduction in their performance at work. Pregnant women with PKU must be particularly vigilant as phe is concentrated across the placenta and literally destroys the foetal brain. A PKU woman off diet when pregnant risks recurrent miscarriages or having a brain damaged child. Prognosis for babies born to PKU women on diet immediately before and during pregnancy is generally good.