Phenylketonuria is a hereditary disease that is expressed in a reduced breakdown of the amino acid phenylalanine. What is insidious about the disease is that if it is present, it has existed since birth and thus leads to an accumulation (accumulation) the amino acid leads.
From around the third month of life, it is present in such high concentrations that it has a toxic effect on the child's mental development. The disease is based on an enzyme defect that prevents the conversion and thus also the breakdown of phenylalanine. In order to excrete the amino acid anyway, it is coupled with various other substances in the body. The excretion of these compounds results in a special, unpleasant odor.
$config[ads_text1] not found
Phenylketonuria is caused by two enzyme defects. The gene with the “blueprint” for the enzymes is located on the twelfth chromosome. To date, several hundred mutations in this gene are known that cause the disease.
Depending on the extent of the mutation, a small percentage of the enzymes can function correctly. Depending on how pronounced the enzyme deficiency is, this leads to a reduced or non-existent breakdown of the essential amino acid phenylalanine. Compared to the normal values, the concentrations in the blood can be 10 to 20 times higher. The frequency varies in different ethnic groups and can be found in around every ten thousandth child in Germany.
The accumulation of phenylalanine then leads to irreparable damage to the nervous system of the children or babies.If the illness is not noticed in time, the child will experience mental retardation (delayed psychological and physical development), which will worsen until the phenylalanine level has been reduced to a normal level.
$config[ads_text2] not foundRead more on the topic: The stages of early childhood development
The inheritance of the clinical picture of phenylketonuria (PKU) follows an autosomal recessive inheritance pattern, i.e. both chromosomes of a chromosome pair must be affected for the disease to become symptomatic. The gene affected, the so-called PAH gene, is located on the twelfth chromosome. Several hundred types of mutations are now known that can cause different forms of phenylketonuria.
The forms vary in the residual activity of the enzyme. This means that certain residual amounts of phenylalanine can still be converted. Most of those affected are there heterozygous (mixed). Put simply, this means that not all cells carry the diseased gene. Only a small proportion of those affected know the genetic defect in all of their chromosomes. There are also regional differences in the types of mutation. Different mutation variants occur differently in certain regions / areas.
Read more on the topic: Genetic diseases
There are also recognizable global differences with regard to the incidence of the disease within the population.
$config[ads_text3] not found
While in Scandinavia and Asian countries about every 100,000 people are affected by phenylketonuria (PKU), countries in the Balkans, for example, show a frequency of up to 1: 5000.
In German-speaking countries, the frequency of phenylketonuria is around 1: 10,000.
The standard diagnosis is made in two different ways, one being the detection of the defective enzyme and the other being the detection of the greatly increased phenylalanine concentration in the blood.
$config[ads_text2] not foundThe first method, known as tandem mass spectroscopy, is part of newborn screening and shows the defect without penylalanine having to be consumed. With tandem mass spectroscopy, over twenty other diseases can be diagnosed quite reliably.
The second method is the Guthrie test (also called the heel test). However, the prerequisite is that the child must have already consumed phenylalanine - for example through breast milk. During the test, some blood is then taken from the child's heel as part of the U2 and examined for its phenylalanine content.
Read more on the topic: U2 examination
The symptoms of phenylketonuria depend to a large extent on how much residual activity of the enzyme is. If there is still a certain percentage of functioning enzymes, the disease is not as pronounced as with a pronounced full-blown phenylketonuria.
Typical symptoms that are noticeable early on are the strong and peculiar smell of the urine of affected children and the mental and psychomotor underdevelopment of the children that occurs over time. If the disease is not detected and treated early, permanent damage to the development of the brain occurs. In the worst case, the children with their intelligence quotient can stay below 50 IQ points.
$config[ads_text4] not found
In addition, phenylketonuria can lead to motor deficits. The important signaling substance dopamine is missing, as is the case with Parkinson's disease. That is why one speaks in this context of so-called juvenile (i.e. adolescent) Parkinson's.
Read more on the topic: When does a baby crawl? - you should know that!
In addition, children with phenylketonuria usually have blonde hair and blue eyes, as their production of the pigment melanin is also impaired.
Read more on the topic: How to recognize behavioral problems in babies
The good news in relation to the therapy of phenylketonuria is that the symptoms of mental underdevelopment can be completely prevented if the therapy is started early. The fundamental building block of therapy is a diet low in phenylalanine, which prevents an accumulation of too much phenylalanine. The later the diagnosis is made and the later the therapy is started, the greater the resulting mental retardation (underdevelopment).
If the disease is not the full picture of phenylketonuria, but a form with reduced enzyme activity, so-called substitution therapy can also be carried out. Those affected are supplied with the molecule tetrahydrobiopterin. This supports the body in converting phenylalanine. The measure of the therapeutic success is the blood concentration of phenylalanine. It should be kept in the range of 2 to 4 mg / dL in people with phenylketonuria.
You might also be interested in this topic: The baby's diet - The recommendation for infants
As already mentioned, the low-phenylalanine diet is the cornerstone of the treatment of phenylketonuria. Since phenylalanine is an essential amino acid, it cannot be completely avoided. This means that babies and toddlers need special infant milk, as normal breast milk contains too much phenylalanine.
It is recommended to continue the diet at least until the age of fourteen in order to ensure the normal mental development of the child. Since phenylalanine is present in almost every animal protein, a low-meat to meat-free diet is recommended for those affected.
The life expectancy of those affected depends on the one hand on the type of phenylketonuria present and on the other hand on the time at which the disease is diagnosed.
$config[ads_text1] not foundWhile a normal age is also possible with a normal variant of phenylketonuria, there are rare variants of the disease that are associated, for example, with a significantly increased potential for convulsions, which can consequently lead to more fatal consequences.
Read more on the topic: Seizure in the baby
In the normal variant of phenylketonuria, however, age is at most slightly affected. However, the time of diagnosis and the start of treatment determine how severe the mental impairment of the sick person is. Mental intelligence therefore has a maximally indirect effect on life expectancy.
The course of the disease also varies, even more, as does life expectancy depending on the form of the disease and the time of diagnosis or the start of treatment.
If the disease is diagnosed in the newborn screening or in the U2 and the low-phenylalanine diet is strictly adhered to, and any substitution that may become necessary is carried out, the disease will hardly appear.
In addition, people who still have residual activity of the affected enzyme have an advantage, as the disease is mild in them, even in the worst case.
However, if the diagnosis is made late, irreversible mental impairment is to be expected, which will continue for life.
Nonetheless, phenylketonuria is not a disease that in western countries means premature death, but rather a normal life expectancy.
A complete cure from the disease is not possible because it is a hereditary disease. The maximum therapy is a diet low in phenylalanine, which results in a reduction in symptoms.
If the disease is recognized early and treated, there are hardly any abnormalities; however, the peculiar smell of the urine and the cell-toxic effect of an excessively high phenylalanine level occur again and again as soon as the diet is avoided. However, since the disease is inherited in a recessive manner, it is unlikely that the disease will be passed on.
