Definition – What is phenylketonuria?
Phenylketonuria is a hereditary disease pattern that is expressed in a reduced breakdown of the amino acid phenylalanine. The tricky thing about the disease is that it has been present since birth and thus leads to an accumulation of the amino acid. From about the third month of life it is present in such high concentrations that it has a toxic effect on the mental development of the child.
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 nevertheless, it is coupled with various other substances in the body. The excretion of these compounds results in a special, unpleasant smell.
Causes of Phenylketonuria
Two enzyme defects are the cause of phenylketonuria. The gene with the “blueprint” for the enzymes is located on the twelfth chromosome. To date, several hundred mutations of this gene are known to cause the development of the disease.
Depending on the extent of the mutation, a small percentage of the enzymes can function correctly. Yes, depending on how severe the enzyme deficiency is, this results in reduced or non-existent breakdown of the essential amino acid phenylalanine. Compared to normal values, blood concentrations can be 10 to 20 times higher.
The frequency varies in different ethnic groups and can be found in Germany in about every ten thousandth child. Due to the accumulation of phenylalanine, the nervous system of the children or babies is sometimes irreparably damaged. If the disease is not noticed in time, a mental retardation (delayed mental and physical development) of the child occurs, which gets worse until the phenylalanine level is reduced to a normal level.
The inheritance of the clinical picture of phenylketonuria (PKU) follows an autosomal recessive pattern of inheritance, i.e. both chromosomes of a chromosome pair must be affected for the disease to become symptomatic. The affected gene, the so-called PAH gene, is located on the twelfth chromosome. Several hundred types of mutations are now known to 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 affected persons are heterozygous.
In simple terms, this means that not all cells carry the diseased gene. Only a small proportion of those affected have the genetic defect in all their chromosomes. There are also regional differences in the types of mutations.
Thus, different mutation variants occur with different frequency in certain regions/areas. Also with regard to the occurrence of the disease within the population, there are globally recognizable differences. While in Scandinavia and Asian countries the incidence of phenylketonuria (PKU) is about one in 100,000, countries in the Balkans, for example, show a frequency of up to 1:5000. In German-speaking countries, the frequency of phenylketonuria is about 1:10,000.
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