Phenylketonuria (PKU): Brain and body abnormalities

In phenylketonuria, an enzyme deficiency causes a build-up of phenylalanine. The brain in particular is affected by the accumulation of this amino acid (building block of proteins). This causes various mental symptoms, such as behavioral problems and intellectual disabilities. In addition, the rare disease is characterized by all kinds of physical signs such as eczema, increased muscle tension and a spreading mouse smell. The symptoms are often not apparent because the disease is easy to detect with a heel prick in a newborn baby. A lifelong low-protein diet in combination with regular medical follow-up prevents serious problems resulting from the disease. If the doctor does not initiate treatment or does not initiate treatment in a timely manner, serious neurological and physical abnormalities will occur with PKU.

  • Synonyms phenylketonuria
  • Epidemiology condition
  • Causes and heredity: Build-up of phenylalanine in the body
  • Symptoms: Damage to brain and body
  • Diagnosis and examinations
  • Treatment through a low-protein diet
  • Disease prognosis
  • Complications PKU
  • Prevention of deviations

Synonyms phenylketonuria

Phenylketonuria is also known under these synonyms:

  • denylalanine hydroxylase deficiency disease
  • oligophrenia phenylpyruvica
  • PAH deficiency
  • PKU
  • Fölling’s disease

Epidemiology condition

The prevalence of phenylketonuria averages between 1 in 10,000 to 15,000 newborns worldwide. The incidence is highest in Turkey with approximately 1 patient with PKU per 2600 births. The disease is also more common in the Yemeni Jewish population, Scotland and Estonia than in other countries. The disease is least common in Finland and Japan. Phenylketonuria has a predilection for people with a fair skin color and people of Asian descent. The diagnosis of phenylketonuria is made just after birth. Finally, the condition has no sexual predilection.

Causes and heredity: Build-up of phenylalanine in the body


Phenylketonuria is a hereditary condition in which an increased concentration of phenylalanine is present in the blood due to mutations (changes) in the PAH gene. Phenylalanine is a building block of proteins (an amino acid) that is obtained through dietary intake. This is present in all proteins and artificial sweeteners (including aspartame and also certain medications). Without treatment, phenylalanine builds up to harmful levels in the body, causing intellectual disability and other serious health problems.


The condition has an autosomal recessive inheritance pattern, meaning that both copies of the PAH gene in each cell must contain mutations for phenylketonuria to occur. Usually the parents, who each contain a copy of the abnormal gene, show no symptoms of the disease.

Symptoms: Damage to brain and body

Most patients have no abnormalities at birth. Normally, the symptoms do not develop even when the diagnosis and treatment is done on time, which is the case in developed countries. Symptoms of untreated or poorly treated PKU do not appear until a child is around a few months old. The increased phenylalanine blood level leads to irreversible brain damage, causing the following mild to severe physical and mental symptoms:


The following physical symptoms are possible with PKU:

  • vomit
  • eczema (chronic skin disease with dry skin and itchy skin)
  • an abnormal position of the hands
  • an abnormally small size of the head (microcephaly)
  • poor growth/bone strength
  • hair loss
  • heart defects or other heart problems
  • hyperkinesia (motor restlessness: increase in muscle activity)
  • pigment poverty (blue eyes (eye color), fair skin, blond hair): Phenylalanine plays a role in the production of melanin, the pigment responsible for skin and hair color in the body.
  • spasticity (increased muscle tension) of arms and legs with a wide-legged gait
  • hypersensitive to light (photophobia)
  • twitching and shaking of one or more body parts
  • tremors (tremors)
  • spread of mouse odor through the skin, mouth and urine, which is a side effect of the excess phenylalanine in the body


The following mental abnormalities are possible with phenylketonuria:

  • aggressiveness
  • anxiety disorders
  • temper tantrums
  • a depression
  • a negative self-image
  • an intellectual disability (main symptom)
  • delayed development
  • epileptic symptoms
  • phobias, mainly agoraphobia (an agoraphobia: intense fear of crowded places or enclosed public spaces)
  • behavioral problems
  • hyperactivity (ADHD: difficulty paying attention and controlling energy)
  • irritability
  • psychiatric disorders
  • self-mutilation

The most severe form of the condition is known as classic PKU. Children and adults with less severe forms of PKU, in which the defective enzyme still retains some function, have a smaller risk of major brain damage. However, most children with this form still require treatment to prevent intellectual disability and other complications.

Diagnosis and examinations

Diagnostic research

There is an increased phenylalanine blood sugar level in the blood. The doctor collects this blood from a baby’s heel (heel prick). The heel prick tests the patient for the presence of various rare conditions, including PKU. Through a urine test, the doctor also notices an increased secretion of phenylpyruvic acid.

Differential diagnosis

The clinical picture of phenylketonuria mimics the symptomatology of these diseases: hyperphenylalaninemia, tetrahydrobiopterin deficiency and tyrosinemia (buildup of amino acid tyrosine in the blood with many symptoms).

Treatment through a low-protein diet

Treatment of patients with phenylketonuria starts within three weeks after the birth of the child. In this way, symptoms and complications can be prevented. The treatment consists of a low-protein diet and regular monitoring of the patient.

Low-protein diet

The main treatment for phenylketonuria consists of a special low-protein diet because foods containing protein contain phenylalanine. The patient should avoid the following foods: potatoes, grains and other vegetables containing proteins, beans, chips, eggs, cheese, chicken, milk, nuts, quorn, beef, soybeans, pork, fish, seeds, aspartame-containing and diet soft drinks are also not recommended. because phenylalanine is released during digestion. Thanks to a special nutritional supplement, no deficiencies occur, but the patient does receive sufficient nutrients that are crucial for growth and general health.

Follow up on illness

In addition, the patient regularly visits a dietician to monitor and possibly adjust the diet. Regular blood monitoring is also necessary because PKU levels change over time, especially during childhood, growth spurts and pregnancy. The doctor always carefully examines any medication use because some medicines also cause an increased phenylalanine concentration.

Disease prognosis

The prognosis is usually very good if the patient adheres to strict nutritional guidelines from shortly after birth. If treatment is delayed or no treatment is given, brain damage will occur. An intellectual disability then occurs before the age of one. Despite treatment, school performance sometimes suffers slightly from the condition.

Complications PKU

Untreated phenylketonuria leads to:

  • major health and development issues
  • an abnormally small head (microcephaly)
  • behavioral, emotional and social problems in older children and adults
  • neurological problems such as seizures and tremors (tremors)
  • irreversible damage to the brain and marked intellectual disability within the first few months of life

Prevention of deviations

An enzyme assay or genetic testing determines whether the parents carry the gene for PKU. Furthermore, chorionic villus sampling or amniocentesis during pregnancy is necessary to screen the unborn baby for phenylketonuria. It is also very important that women with PKU receive regular follow-up and adhere to their diet, especially during pregnancy. A buildup of phenylalanine harms the developing baby, even if the child does not inherit the defective gene. In addition, the mother has a higher chance of miscarriage.