What is Phenylketonuria?

Phenylketonuria (PKU) is the most frequent amino acid metabolism disorder. It is caused by a complete lack or limitation of phenylalanine hydroxylase (PAH) functioning. This enzyme is responsible for converting phenylalanine into tyrosine. Such chemical reaction takes place in liver cells, i.e. hepatocytes (fig). Phenylalanine is found in dietary fibre that is consumed every day (phenylalanine constitutes 3-7% of dietary fibre). Food products rich in protein such as meat, fish, eggs, milk and milk products, cereal products, nuts, cocoa and chocolate, soy, beans and pea, contain particularly large amounts of phenylalanine. The treatment is based on following a phenylalanine-restricted diet, i.e. low-phenylalanine diet.  Phenylalanine metabolism disorders cause the concentration of this amino acid in blood to rise. Blood carries phenylalanine to the central nervous system which receives permanent damage. This leads to various forms of mental retardation and neurological disorders that are main symptoms of untreated or insufficiently treated PKU. Children who are diagnosed with this disease in the first days of their lives and systematically treated over a long period of time (preferably until death), grow normally and can fully use their potential. Patients successfully reach subsequent educational levels, graduate from schools, colleges and universities, perform many jobs and have happy families.


In Poland, PKU is diagnosed in 1 in 7000-8000 live newborn, which means that every year 60-70 PKU-affected children are born.  This genetic disease is passed to children by both parents. It is inherited in autosomal recessive mode, which means that a child must receive 1 mutated gene causing PKU from each parent. For the disease to appear, two mutated genes are needed. Usually, parents are just carriers of the faulty gene, they show no symptoms and are unaware of the fact that they may pass the disease to their children. They are healthy because their second gene is „healthy”. In Poland, 1 in 46 people is a healthy carrier of the faulty PKU gene. There is a 25% risk that all children from carrier parents who show no symptoms will be affected. Having one ill child does not imply that next children will be healthy – the risk of passing the disease is constant and it reaches 25% for every child. Therefore, it is frequent that in one family, two or even three children suffer from PKU. However, if one parent has PKU, and the second parent is an asymptomatic carrier, the risk of having an affected child is 50% for each pregnancy. If both parents have the disease, the risk of having an ill child is 100%.


It has been known for many years that in order to treat PKU effectively, the disease must be diagnosed early and dietary treatment must be applied as soon as possible. PKU diagnostics is based on performing the so-called screening of newborns. This allows to diagnose the disease in the first days after the birth. It is carried out by sampling a few drops of blood from a heal of every newborn when it is 72-hours old and identifying the phenylalanine levels. In Poland this is done by a colorimetric method. For the test to be correct, the child must be breastfed or fed with modified milk before. Sometimes it is necessary to repeat the test if a child was born prematurely or is ill, especially if it is fed parenterally. In healthy children, the phenylalanine levels are usually below 2 mg%, in ill newborns the levels are much higher and often exceed 20mg%. Higher level of phenylalanine requires deeper diagnosis and numerous tests. Therefore, the parents may receive a call to the hospital even after a few days of the child’s stay at home. These tests are to establish the PKU type and exclude the so-called unusual forms of disease related to lack of PAH co-factor (i.e. tetrahydrobiopterin) activity. This rare (1 to 3%) type of phenylalanine metabolism disorder is a serious systemic disease causing numerous neurological complications and requiring different forms of treatment than PAH. In most cases, however, one of three typical forms of PAH deficiency is diagnosed:  •mild hyperphenylalaninemia (blood phenylalanine concentration: up to 10 mg%), which does not require treatment (unless the patient is a woman planning pregnancy or already pregnant), •mild PKU (blood phenylalanine concentration: between 10 and 20 mg%), •classical type of disease (blood phenylalanine concentration: above 20 mg%).  The type of disease most popular among Polish children is classical PKU related to complete or almost complete enzyme inactivity. Both the mild and classical types of the disease require immediate introduction of a diet (preferably before the end of the 2nd week of life), which is currently the standard proceeding in case of PKU.  It is also possible that first test results are abnormal, but later tests show that the phenylalanine levels have normalized. Such case is called temporary hyperphenylalaninemia, which is usually an effect of a temporary lowering of enzyme production in the liver. Such children do not require dietary treatment.  One should remember that PKU children are born with a healthy CNS. During pregnancy, the mother’s healthy liver (even if she is a PKU carrier) ensures proper phenylalanine metabolism for the foetus. In the first days of life, the blood phenylalanine concentration in a breastfed child or child fed with modified milk raises enough for the screening tests to detect the disease. Fortunately, the time needed for diagnosis is so short that no brain damage occurs. Children that are treated early develop properly. However, one should not delay visiting the hospital and starting treatment as its success strongly depends on the age at which phenylalanine-restricted diet was introduced. The sooner, the better for the child’s development.


SOURCE: http://www.shs.com.pl/choroby.php?source_id=1213&sys_id=126