Phenylketonuria is an inherited metabolic disease that causes severe brain damage without treatment. Read all about it!


The phenylketonuria (PKU) is a congenital hereditary disease of protein metabolism. It prevents the degradation of the amino acid phenylalanine. This accumulates in the body and disturbs the child's development of the brain. Left untreated, phenylketonuria causes severe mental disability. But with timely therapy, patients can live a normal life. Find out all about phenylketonuria here!

ICD codes for this disease: ICD codes are internationally valid medical diagnosis codes. They are found e.g. in doctor's letters or on incapacity certificates. E70

Product Overview


  • description

  • symptoms

  • Causes and risk factors

  • Examinations and diagnosis

  • treatment

  • Disease course and prognosis

Phenylketonuria: Description

Phenylketonuria (PKU) is an inherited metabolic disease that is inherited from birth and interferes with the breakdown of the essential amino acid phenylalanine. Amino acids are the basic building blocks of proteins and thus vital metabolic components. Some of them can enter the body only through food, the organism can not produce them. Such amino acids are called essential.

What happens with phenylketonuria?

Normally, amino acids are subject to a balance between uptake / build up and degradation, so there is always as much as the body needs. For different amino acids, a deficiency or excess can cause significant damage and various symptoms.

In classical PKU, the effect of phenylalanine hydroxylase (PAH) is limited or even completely absent. It accumulates by the PAH deficiency increasingly phenylalanine in the body. Too high a concentration of phenylalanine significantly interferes with brain development and early on leads to mental disability in the young patients.

Because in the disease, the normal degradation of phenylalanine is not possible, other degradation products, called phenyl ketones. They are excreted in the urine and are responsible for the name of the disease.

Atypical phenylketonuria

Even in atypical forms of phenylketonuria, the degradation of phenylalanine is disturbed. However, the cause is not a defect of PAH. Instead, the function of a coenzyme, tetrahydrobiopterin (BH4), restricted. It is indirectly involved in the degradation of phenylalanine because PAH requires BH4 for the conversion of phenylalanine to tyrosine.

Because BH4 also important for the production of the messengers dopamine and serotonin is an atypical phenylketonuria with BH4Lack usually more complicated than the classical form.

Who concerns a phenylketonuria?

PKU is one of the most common congenital metabolic diseases. It is estimated that around 7,000 newborns around the world suffer from it, with no difference between girls and boys. Because it is a hereditary disease, often several members of a family are affected.

Phenyketonuria: symptoms

First, babies with phenylketonuria do not show disease symptoms. Only in the fourth to sixth month of life, first problems appear, if the disease has not been recognized and treated until then. Especially the disturbed brain maturation causes massive complications. Symptoms of an untreated PKU include:

  • a strong intellectual developmental backlog. Brain damage progresses to puberty and then stagnates. The affected children are then mostly severely mentally handicapped.
  • Seizures (epilepsy). Because of the damage, the nerve cells of the brain are particularly sensitive and overexcitable. Frequent epileptic seizures are the result.
  • motor disabilities. Not only the brain cells, but also the muscles of the patients is over-excitable. Therefore, it often spasmodic (spasticity), which leads to various movement disorders.
  • Behavioral disorders. Some children with phenylketonuria are hyperactive and unusually aggressive, and anger is more prevalent.
  • a small head (microcephaly). Because the patient's brain does not develop properly, head growth also remains. Especially in older children, the small head circumference in comparison to the peers on.
  • a noticeable smell. PKU produces certain breakdown products of phenylalanine, which smell similar to mouse droppings. These substances are excreted mainly in the urine, but sometimes also via the skin.
  • eczema-like skin lesions

Because phenylketonuria also interferes with the production of the pigment pigment melanin, many sufferers have very light, sun-sensitive skin and white-blond hair. Also, the iris of the eyes is light blue to transparent and lets the reddish fundus shine through.

The PKU symptoms are individually different pronounced.Above all, this is because the activity of phenylalanine hydroxylase (PAH) is differently restricted in each patient. Some still have some residual activity, so less phenylalanine accumulates in the organism. Others show no enzyme activity - the disease progresses correspondingly faster and more seriously.

Phenylketonuria: causes and risk factors

Phenylketonuria is a hereditary disease. There are now numerous genetic mutations known that lead to a defect of PAH. The type of mutation determines how much phenylalanine degradation is limited.

The inheritance of a PKU is recessive, which means that a person can be carriers of an altered gene, without him getting the disease. Likewise, people with phenylketonuria can produce healthy children.

Only if both parents have corresponding mutations in the genetic material, there is a certain probability that their offspring will develop a phenylketonuria. If both parents are not only carriers of the disease, but are also suffering from PKU, all of their children will also be affected.

Phenylketonuria: examinations and diagnosis

Since it is possible to prevent the serious consequences of phenylketonuria when starting treatment on time, it is particularly important to discover the disease as early as possible. In Germany, children are examined on the third day after birth as part of a general examination (neonatal screening) for various congenital diseases, including PKU.

Tandem mass spectrometry

Meanwhile, many congenital metabolic disorders are diagnosed using so-called tandem mass spectrometry. It makes it possible to examine the blood of the newborn easily and quickly. Within a few minutes, physicians can detect more than 20 other diseases besides phenylketonuria.

Guthrie test

Also named after its inventor Guthrie test allows the diagnosis of a PKU. To do this, remove a small amount of blood from the heel of children and apply it to a piece of filter paper. In the laboratory one can then determine whether the concentration of phenylalanine is increased.

The Guthrie test was introduced in the 1960s and has long been the standard method for detecting phenylketonuria. But it has disadvantages compared to tandem mass spectrometry. Thus, the Guthrie test delivers only after five days, a result that is also error-prone. For example, factors such as diet or possible antibiotic therapy of the child distort the results. In some countries, the Guthrie test is still in use, in Germany it is usually no longer used.

Other tests

If neonatal screening leads to the suspicion of phenylketonuria, another investigation will follow. With this one can determine at the same time the exact concentration of phenylalanine in the blood.

Finally, it remains to be distinguished whether it is a typical (classical) or atypical PKU. Also available are special tests such as the tetrahydrobiopterin challenge test. The distinction is important because an atypical phenylketonuria is treated differently than the classical form.


A phenylketonuria can already be detected during pregnancy (prenatal diagnosis). In addition, a small amount of amniotic fluid is taken from the mother's amniotic sac and the cells of the unborn child are examined. Any genetic defects that cause a PKU can thus be determined.

With neonatal screening, a phenylketonuria is usually discovered early enough to be treated. Because an amniocentesis examination always involves a certain risk, its use to diagnose a PKU usually makes no sense.

Phenylketonuria: treatment

There is only one way to counteract the excess of phenylalanine in a PKU: The affected children must follow a special diet to take as little phenylalanine with the food. In addition, they need certain dietary supplements to replace substances that would be produced in healthy children from phenylalanine.

The therapy must begin before the first symptoms of a developmental disorder occur, ie within the first two months of life. Already occurred brain damage can not be undone.

Nutritional therapy with the PKU diet

All natural proteins consist of about five percent of the amino acid phenylalanine. In most foods is thus far more of it than the body needs. For a healthy person this is not a problem because it breaks down and excretes the excess amount of phenylalanine.

Patients with phenylketonuria, on the other hand, have to do without natural proteins for the most part. Industrially manufactured special products replace the missing food components. On the one hand, one wants to prevent such an excess of phenylalanine, on the other hand, to supply to the patients those substances which would otherwise be lacking, such as, for example, tyrosine, which is formed from phenylalanine.

The goal of the PKU diet, however, is not to completely stop the intake of phenylalanine.Because a certain amount of the amino acid needs the organism for important metabolic processes. Achieving the right concentration poses a great challenge for physicians and patients and requires a lot of discipline.

The diet must therefore be followed for a lifetime, but strictly until the age of six. Because the brain develops very strongly up to this age and is therefore particularly susceptible to damage. In adulthood, high levels of phenylalanine do not cause brain damage, as in children. But they can be the trigger for other neurological disorders such as concentration disorders or a slowing of the reaction.

Phenylketonuria diet treatment should begin in a Metabolic Disease Center. Because not in every hospital it is possible to instruct the parents in the diet. This is best done with the help of a diet consultation that shows how to do the diet and regularly monitor phenylalanine blood levels.

Treatment of atypical phenylketonuria

Atypical forms of PKU artificially replace the missing coenzyme BH4 as well as certain messenger substances such as dopamine and serotonin. In some cases, the patient must additionally follow a diet low in phenylalanine.

Phenylketonuria during pregnancy

If you are pregnant and you are suffering from phenylketonuria yourself, you should consider the following:

  • Keep your diet particularly strict!
  • Get your phenylalanine blood levels determined at short intervals. Because the concentrations of phenylalanine are about twice as high in the unborn child as in pregnant women. In addition to the brain, they can also harm the heart and eyes of the unborn child. Abnormalities of the child's skeleton can also arise from a high level of phenylalanine during pregnancy.
  • To prevent brain damage to the baby in early pregnancy, women with phenylketonuria should plan a pregnancy well and provide it from the beginning.
  • In pregnant women with phenylketonuria, a diet that is not strictly followed may sometimes lead to a miscarriage (spontaneous abortion).
  • In any case, pregnant women with phenylketonuria should be advised and instructed by a doctor.

Read more about the investigations

  • U examinations

Phenylketonuria: disease course and prognosis

Early prognosis of phenylketonuria, if possible already in the newborn, and if the specific PKU diet is followed, the prognosis is usually good. The children develop mentally normal and have an average life expectancy.

In contrast, brain damage leads to severe mental development disorders that can not be compensated later. Although those affected have a normal life expectancy, their intelligence quotient is almost always well below the norm.

A special case is the rare atypical form of phenylketonuria, in which aBH4Lack exists. This variant of the phenylketonuria despite diet can lead to progressive neurological damage with severe cramps.

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