Phenylketonuria: What is it and how is it manifested? (hyperphenylalanemia)

The disease is also called PKU (phenylketonuria) according to its abbreviation. It is a hereditary disease, which is caused by a gene mutation. This in turn causes the absence of an enzyme that converts the amino acid phenylalanine.

Phenylalanine accumulates in the body, especially in body fluids. Excessive amounts cause the development of mental retardation as well as physiological symptoms. The cause is damage to nerve fibers and interference with metabolic processes. Under normal circumstances, phenylalanine is converted to tyrosine.

The disease was first recorded in 1934. It is an autosomal recessive disease. Thus, for an outbreak, the damaged gene needs to be inherited from both parents.

In this case, if both parents are carriers of PKU, the risk of disease outbreak is 25% and the risk for its carrier is up to 50%. However, there is also a 25 percent chance that the child will not develop the disease and will not be its carrier.

It occurs in about one in 6 to 10,000 newborns . But the incidence rate depends on the geographical location. For example, in Italy and Ireland, the incidence is higher and, conversely, in Finland and Japan, it is lower. In such Turkey, the prevalence of the disease is as high as one in 4,000.

The disease already develops in children. As soon as they start taking in milk, their phenylalanine levels rise. Due to the excess, it starts to damage the brain. Thus, psychomotor retardation begins to develop during infancy.

The child is also restless. Already between the 6th and  12th months are with him can appear seizures. Children are pale, have light hair and blue eyes. The skin is prone to eczema. Phenylalanine is also excreted in the urine, which then typically smells.

However, thanks to neonatal screening, the disease can be detected relatively quickly. However, due to the possibilities of modern medicine, the prospects for a better quality of life are relatively high. Of course, consistent treatment and a positive attitude and activity on the part of the parent are needed.

The damage occurs in the phenylalanine hydroxylase (FAH) gene. The locus is located on chromosome 12. And it is reported that we know about 400 mutations in a given gene.

What is phenylalanine?

Phenylalanine is an essential amino acid. The label is essential because the body cannot make it itself and must receive it from the diet. It is important because it serves to transmit nerve impulses.

Phenylalanine is converted to tyrosine by the enzyme phenylalanine hydroxylase (FAH). Tyrosine is then used, and very important, in the production of neurotransmitters. It forms dopamine, adrenaline, norepinephrine, thyroxine.

It also partially forms melanin, which serves as a skin pigment. In adults, it then consists of about 10% phenylalanine. This residue is used to make proteins. In children, the ratio is different, with up to 60% being used for protein production. 

It is part of all living organisms, in the form of protein. The highest proportion of phenylalanine in the diet is in:

• chocolate
• cheese
• nuts
• seeds
• milk
• eggs
• meat
• soy, tofu
• it is also used in artificial sweeteners

Phenylalanine has several good properties, such as:

• improves memory
• adds resistance to stress
• supports mental condition
• promotes sexual activity
• It is used for diseases such as Parkinson's, Multiple sclerosis, rheumatoid arthritis, or mental disorders

Phenylketonuria is the most common recessive inherited disease. It is caused by a defect in the gene (12q22-q24.2), which causes the absence of an enzyme called phenylalanine hydroxylase (FAH). The enzyme may be completely missing or inadequate.

This enzyme is responsible for several metabolic processes in the body. In particular, however, it converts the amino acid phenylalanine to tyrosine. When this enzyme is not present in the body, phenylalanine accumulates in body fluids and therefore in the blood. This causes problems in the central nervous system, as its high levels in the body are toxic. 

Subsequently, CNS disorders occur, which are manifested mainly by mental retardation or other brain functions. Attacks of muscle cramps are also associated. There are also problems with pigmentation, as part of the phenylalanine is used in the formation of melanin.

In excess, phenylalanine is excreted in the urine, from which the name phenylketone is derived.

The result is a lack of tyrosine. This is replaced by increased dietary income. Tyrosine is an amino acid. It is important in the production of hormones such as adrenaline, norepinephrine, dopamine, but also thyroxine.

Tyrosine is not an essential acid, so the body can make it itself. However, only if he has enough phenylalanine, and therefore FAH. Its sources are mainly almonds, kernels, sesame, bananas, and avocados, but also dairy products.

The disease manifests itself physiologically, ie physically and mentally. Mentally, mental illness develops from an early age when the disease is not treated. The onset of the disease is immediately after the use of milk.

Phenylalanine accumulates in the body. This damages the CNS and results in difficulties. When left untreated, children have a reduced IQ. And on the verge of imbecility or idiocy. Usually, the disease reduces IQ to half its original value.

The first symptoms develop from the 2nd month. However, they will be fully manifested between the 6th and 12th months. In addition to mental retardation, memory problems are associated, and children are hyperactive. From a psychological point of view, in addition to mental retardation, there is also instability in children's behavior, which can sometimes be apathetic, sometimes restless, and also aggressive.

Of the physiological manifestations, vomiting or vomiting are also typical. The disease is also characterized by reduced skin pigmentation. Overall, the skin is pale,  dry and the hair is pale and the eyes are mostly blue. The skin is prone to eczema or rashes.

In addition to paleness, from a physiological point of view, the disease also causes poor tooth development, flat feet, spinal movement disorders, and muscle stiffness. Damage to the central nervous system causes seizures.

Elevated levels of phenylalanine lead to its excretion in the urine. This causes typical smelly urine, as if from a mouse. The disease can also cause growth retardation, microcephaly, which is a visibly reduced brain part of the head compared to the facial part.

The disease can take many forms. The most common form is classical phenylketonuria. Subsequently, moderate and light forms are also known. The mild type is also referred to as hyperphenylalaninemia.

Symptoms that occur with phenylketonuria:

• mental retardation, up to the severe degree of treatment failure
• seizures
• microcephaly
• memory disorders
• mental disorders, aggression, hyperactivity
• reduced pigmentation, ie pale skin, and hair, blue eyes
• vomiting
• gargling
• eczema
• smelly urine after a mouse
• growth slowdown, lower growth
• involuntary movements

The disease can be detected in our country for more than 50 years. Postpartum screening examinations are performed after delivery. Blood tests for the presence or absence of the enzyme FAH, which converts amino acids to tyrosine. Genetic tests are also performed to confirm the diagnosis.

In addition, symptoms may be observed in a later child. Such as muscle cramps. EEG is also used to record the electrical activity of the brain, which can detect psychomotor retardation in time.

The disease begins immediately after the start of milk intake. Phenylalanine begins to accumulate and from about the 2nd month first symptoms may appear. The manifestations are fully highlighted between the 6th and 12th months. 

As soon as the newborn starts drinking breast milk, the amino acid levels increase and, unless they are enzymatically broken down, the brain is damaged. And thus to the development of mental retardation.

Older children develop hyperactivity, memory disorders, and behavioral disorders. The child is restless, he can be aggressive. However, the lag in development is visible between the 4th and 9th months of life. The slowdown in development is also manifested by microcephaly, which is a smaller proportion of the brain part of the head compared to the facial part.

As amino acid levels rise, damage to the central nervous system worsens. External physiological manifestations of the disease are already visible. Such as cramps, routes, or involuntary movements, but also intense vomiting.

Children are pale due to reduced skin pigmentation. Similarly, hair is pale and eyes have blue irises. The skin is sensitive, eczema or other rashes are formed to an increased extent. In addition to muscle cramps, muscle stiffness is present.

Elevated levels of phenylalanine are also reflected in its urinary excretion. It then has a typical mouse odor. Which is also noticeable in sweat, ie leather. There are effective measures and treatments against these symptoms. We provide information about them in the treatment.

Food and phenylketonuria

As mentioned, a dietary regimen should be followed in phenylketonuria. Protein is found in most foods, which means that, as with celiacs, dietary adjustment is needed in this disease.

The diet will include food supplements, both special amino acid mixtures. These are taken every day to maintain the required daily protein intake. These are important building blocks in the body.

Specially prepared foods and foods with a minimum protein content that are weighed are suitable to control intake. Some foods may be in the diet after calculation, for example:

• potatoes and products thereof
• cauliflower
• cabbage
• spinach
• ketchup
• mustard
• and other low protein vegetables and fruits

In the infographics, we present a brief overview of the representation of unsuitable and suitable foods. There are also precise food tables for this disease, which facilitate the choice of diet and a dietitian will advise you when compiling a diet.