What is Phenylketonuria (classical, mild), symptoms and treatment


What is phenylketonuria?

Phenylketonuria is a rare  genetic disease , identified by the accumulation of phenylalanine due to the defect or absence of the hydroxylase enzyme. It is essential for the conversion of the amino acid into tyrosine, a protein active in the synthesis of melanin.

This hydroxylase mutation is autosomal and recessive, that is, it affects men and women in the same proportion and is induced by the recessive genes of the individual’s parents.

The genetic alteration inherited by both parents triggers a defect in the coding of the enzyme phenylalanine hydroxylase (PAH), essential to transform the amino acid phenylalanine (FAL) into another amino acid, tyrosine.

Since people with the disease are unable to metabolize phenylalanine, FAL accumulates in the bloodstream. With this increase, the blood molecules are transformed into phenylpyruvic acid, which becomes toxic in several organs, including the brain.

The highest rates are found in Turkey (1 out of 2,600 newborns), Ireland (1 out of 4,500 newborns), and the lowest in Finland, Japan and Thailand (1 out of 200, 1 out of 143,000 and 1 out of each 212,000, respectively).

Brazil is not found on any of the extreme points, with 1 in every 25,000 newborns.

Why is phenylalanine toxic to phenylketonurics?

Phenylalanine is toxic because, despite being naturally present in the body, phenylalanine hydroxylase needs to act on it, so that it is transformed into the amino acid tyrosine.

Therefore, as phenylketonurics are born without this enzyme or with changes that impair its proper functioning, phenylalanine accumulates in the blood and is converted into toxic compounds, such as pyruvic acid. This acid is a component found in urine and sweat, and when it migrates to the brain, it affects the neurological system.


Its cause is genetic. Because it is an autosomal recessive genetic disease, it is necessary for both parents to have the recessive gene and pass it on to their child.

This disease is present in approximately 1 in every 10,000 people born alive in the Caucasian population. PKU carriers have a genetic mutation in phenylalanine hydroxylase.

This mutation can occur in any of the DNA bases within the affected gene, and different mutations have unequal effects on the enzyme. A good example is a change that causes accelerated catabolism, which consists of a high rate of degradation of the enzyme.


Because it is a genetic disease, it is only passed from parents to children, so there is no risk of contracting the condition when living with phenylketonurics. That is, the disease is not transmissible.

Groups of risk

The incidence of the disease varies according to ethnic groups, with Caucasians  (whites) being most affected by the disease. So far, it is not known for certain why this group is the most affected.


As rare as this condition is and with an average of 1 to 10,000 newborns, there are still 3 types of phenylketonuria, with a variable incidence between nations and ethnic groups worldwide.

Regardless of which region suffers most from phenylketonuria, they are:

Classical phenylketonuria

In classical phenylketonuria, known as the most serious of the disease variants, the activity of the enzyme phenylalanine hydroxylase is almost absent, that is, it is below 1%. As a result, plasma phenylalanine levels are above 20mg / dL.

Phenylacetonuria juice

In the second variant of the disease, the enzyme activity is 1% to 3%, so the plasma levels of phenylalanine are between 10 to 20 mg / dL.

Transient or permanent hyperphenylalaninemia

Although the name is the most complicated to pronounce, this is the mildest form of the disease.

It occurs when the enzymatic activity is higher than 3% and the phenylalanine levels are between 4 to 10mg / dL. Many times, no therapy is implanted to patients, as there are few studies on it, since it is considered the mildest form of the disease.

For girls with transient hyperphenylalaninemia, the ideal is that, when starting the childbearing age, start the diet for phenylketonuric patients because, in case of pregnancy, their children have a greater chance of malformation than the other groups.

Synthesis of phenylacetonuria

When the diagnosis is not made soon after birth, the symptoms of phenylketonuria appear at around 4 or 6 months of the baby’s life. Those frequently reported are:

  • Skin wounds, similar to eczema (skin inflammation);
  • Characteristic body odor;
  • Sickness;
  • Vomiting;
  • Aggressive or self-aggressive behavior;
  • Hyperactivity;
  • Mental retardation, usually severe and irreversible;
  • Convulsions.

How is the diagnosis of phenylketonuria made?

As phenylketonuria is a metabolic disease from birth, it is at the moment when the baby is born that the diagnosis is made. It must be performed from 48 hours after birth until the 5th day of life.

Foot test

The examination responsible for this is the famous little foot test , and no, we are not talking about that foot stamped on the baby’s card, but an examination made from the blood collected from the baby’s heel.

The health professional, usually the nurse, sterilizes the baby’s heel and then punctures the area. Because it is a highly vascularized site, blood flows quickly, being collected on a filter paper with demarcated circles. The paper must not come into contact with the baby’s skin.

In the laboratory, experts analyze and detect possible diseases. In addition to phenylketonuria, the diseases that can be revealed through the test are:

  • Hypothyroidism;
  • Congenital adrenal hyperplasia;
  • Cystic fibrosis;
  • Biotinidase deficiency;
  • Congenital toxoplasmosis;
  • G6PD deficiency;
  • Congenital rubella;
  • Sickle cell anemia;
  • Chagas disease.

Blood test

Children who have not undergone the heel prick test at the maternity hospital may be diagnosed with the disease through a blood test  and based on the symptoms presented.

Blood tests will always be a constant in the lives of people with phenylketonuria. It should be repeated every week until the baby is 1 year old, every 15 days between 2 and 6 years old and monthly from 7 years old.

Check below the reference values ​​for the examination of phenylketonuria.

Up to 7 years old8 mg/dL
After 7 years of age10 mg/dL

Phenylacetonuria tem cura?

No, phenylketonuria has no cure . Because it is a rare metabolic genetic disease, it is incurable. However, treatment can help to combat symptoms and complications.

What is the treatment for phenylketonuria?

The treatment consists of a nutritional regimen, which aims to avoid phenylalanine or consume it in the smallest amounts possible. Since phenylalanine is an amino acid found in protein- source foods , people with the disease cannot consume various foods of plant and animal origin, such as:

Animal foods

  • Meats;
  • Milks and derivatives;
  • Eggs;
  • Fish;
  • Seafood;
  • Meat products such as sausage, sausage, bacon and ham.

Plant-based foods

  • Wheat;
  • Soy and derivatives;
  • Chickpea;
  • Bean;
  • Pea;
  • Lentil;
  • Chestnuts;
  • Peanut;
  • Nuts;
  • Almonds;
  • Hazelnut;
  • Pistachio;
  • Pinion.

Phenylketonurics, in addition to not being able to consume any of these foods, should avoid foods with aspartame, which is a very common sweetener in the production of soft drinks, food sweeteners, ready-made spices, mayonnaise, yogurts, etc. Not ingesting any product that has one of the above ingredients is also essential.

To complement the diet, the nutritionist recommends a special formula that supplies tyrosine and several other amino acids that are no longer ingested in the diet. This supplement resembles a special milk and must be ingested throughout the life of the phenylketonuric.

Very recently, soluble tablets started to be commercialized with these nutrients, but they are still not popular in Brazil.

If the carrier of the disease consumes only the recommended amounts of phenylalanine, his motor and cognitive development will not be affected. The amount allowed varies according to the age and weight of each patient. The allowed values ​​are:

AgeQuantity per day
0 to 6 months20 a 70 mg/kg
From 7 months to 1 year15 a 50 mg/kg
From 1 to 4 years15 a 40 mg/kg
From 7 onwards15 a 30 mg/kg

The nutritional diet varies from case to case and also at each stage of life. See below for care for each stage of life.


Breast milk has phenylalanine, so it is not recommended that the mother breastfeed the baby with him frequently.

The pediatrician will indicate at what times the parents should breastfeed the baby and when he will have to ingest artificial formulas that do not contain phenylalanine, but that are nutritious, for the rest of the day.

The commonly indicated formulas are:

  • PKU Med A;
  • PKU Med B;
  • PKU Med C;
  • PKU Med Anamix;
  • PKU 1, 2 and 3;
  • PHENYL – Free 1 e 2.

There are so many variants because each formula is used according to the baby’s age, weight and digestion capacity. This is the reason why each individual must have their own diet prescribed by the nutritionist.

When parents do not take proper care of the baby’s feeding, the symptoms that commonly manifest are:

  • Growth delay;
  • Frequent itching of the skin;
  • Urine, my breath smells of mold;
  • Very light skin;
  • Small head, incompatible with body size.

Early solid nutrition and childhood

At this stage, it is common for nutritionists to continue advising the consumption of special milk, in order to be able to supply the amount of nutrients and vitamins necessary for healthy child development .

It is at this stage that the child begins to feel the desire to consume foods that are harmful to his health, so the monitoring of parents must be present.

Below is an example of a menu for a three-year-old child with phenylketonuria:

Menu Amount of phenylalanine
300 mL of special milk60 mg
3 tablespoons of cereal15 mg
60 g canned peach9 mg
230 mL of special milk46 mg
Half a slice of bread with low protein content7 mg
A teaspoon of jam0
40 g of cooked carrot13 mg
25 g of pickled apricots6 mg
4 slices of peeled apple4 mg
10 cookies18 mg
Special milk46 mg
Special milk46 mg
Half a cup of low-protein pasta5 mg
2 tablespoons of tomato sauce16 mg
2 tablespoons of cooked green beans9 mg
Total300 mg

It is extremely important that, before consuming the food, the individual and his family check on the product labels whether the food contains phenylalanine or not and what is its content, so that they can be adjusted according to their diet.


In the adolescence stage, the permitted levels of phenylalanine in the blood become slightly higher, but care should in no way be left aside, but maintained with the same vehemence as the moments already lived. Thus, adequate growth is maintained.


Again, the blood will tolerate a higher level of phenylalanine, but the diet should continue to be maintained to avoid problems such as seizures , nausea and vomiting.


If medical monitoring in the life of a phenylketonuric is already constant, in pregnancy it is even greater. High values ​​of phenylalanine in the blood, besides being harmful to the mother, can bring risks such as cardiac malformation, mental retardation and microcephaly to the baby.

The damage to the baby may increase if the mother has transient hyperphenylalaninemia phenylketonuria, since the increased amounts of the mother’s FAL lead to a higher incidence of mental disability (21%), microcephaly (24%) and low weight at birth (13%).

Medicated para phenylcetonuria

There are no medications that can help in the treatment of phenylketonuria, quite the opposite: some medications can even aggravate the condition.

In view of this, it is of the utmost importance never to self-medicate . Always consult your doctor and tell him in detail your conditions, so he will prescribe only what is appropriate for your clinical condition.

However, studies have already started to be carried out to try to develop a drug that can supply the enzyme hydroxylase. However, there are more than 200 different genetic mutations associated with the disease, so it is difficult to establish a pattern that completely compensates for the deficiency of the enzyme.

Living together

Because it is an incurable disease, there is nothing the person with the disease can do in a definitive way to get rid of it. However, it is possible to live with the disease when you have a careful diet.

In order to live with phenylketonuria, it is necessary to be carrying out frequent examinations, with the following doctors:

  • Neurologist: evaluates the nervous system;
  • Nutritionist: to have an adequate diet;
  • Pediatrician: when phenylketonuric is still a child;
  • Psychiatrist: if the patient presents psychological disorders;
  • Geneticist: studies the genes and helps patients deal with the disease;
  • Pedagogue: instructs education professionals in relation to the disease, helps to promote the insertion of the individual in school;
  • Social worker: analyzes and assists the social, cultural and economic profile of families;
  • Psychologist : aims to generate actions and activities aimed at the adherence of the child and the family in the treatment.

In order to adapt to the disease in the best possible way, it is necessary to know that the treatment varies according to the individual’s age group, which is why the constant need to attend specialists regularly.

From 2 years of age the brain develops more quickly, and from this age onwards the complications of the disease begin to manifest, if the diet is not being done correctly or is deregulated in the face of the patient’s needs. Check below the minimum required periodicity.


  • Up to 6 months of age: once a week;
  • From 6 months to 1 year: once every 15 days;
  • From 1 year to 2 years: once a month;
  • From 2 years: The interval between one consultation and another is variable. The most common is that they are done every two months.

Pediatrician and Geneticist

  • Up to 1 year: once a month;
  • From 1 to 2 years: once every 2 months;
  • From 2 years: once every 6 months.

The family in the treatment

It is not easy to make children eat what their parents ask, but in the case of phenylketonuria, this is essential for the child to have a good quality of life and, especially, to avoid complications.

The family must always be well informed about the disease, so they will be able to provide children with the necessary care.

It is necessary for parents or guardians to make it extremely clear to the child what their limits are and that any action they take will have a consequence, be it positive or negative.

Hiding the food that the child cannot eat is not a good tactic, because in addition to increasing his desire, it does not teach the child to understand his limits, which is extremely important since he will enter into contact with other people soon and will be exposed to all types of food.

Another important point is to know that the damages are not identified instantly, so many parents end up letting their children run away several times from the diet established by the nutritionist. Some even think that the doctor is exaggerating his instructions. However, such foods are bad for the child, yes, and a lot!

If someone from the family does not understand the risks that banned foods bring and insists on offering them to the child, the parents can invite the relative to one of the consultations, where the doctor will explain why this behavior is putting the child’s life at risk .

When the family is united for a greater cause (in this case, the child’s health), the treatment becomes much simpler and the results are more effective. This is because an environment is created in which everyone collaborates with the diet, instead of just a family member trying to control the situation and end up being demonized by others.


The importance of an early diagnosis is due to the complications that a phenylketonuric can acquire if its levels of phenylalanine in the blood are not within the indicated by the doctors. The accumulation of this amino acid can generate:

  • Delay in psychomotor development;
  • Little brain development;
  • Microcephaly;
  • Hyperactivity;
  • Behavioral disorders;
  • Decreased IQ;
  • Serious mental deficiency;
  • Convulsions;
  • Sickness;
  • Tremors;
  • Vomiting;
  • Early emergence of neurological diseases;
  • Possible depression, attention deficit and irritability.

As time passes, there may be difficulties in sitting and walking. Behavioral disorders, speech and intellectual development in general will also be presented. As if that were not enough, individuals can still develop depression , ataxia and epilepsy .

When it comes to phenylketonuria, if a region of the brain is affected by the accumulation of toxins, the individual can start to correctly follow a balanced diet and there will be no use in the injury already caused, as this type of injury is permanent . However, if you follow the diet correctly, other lesions will not appear.

Como prevenir a phenylcetonuria?

There are no ways to prevent the disease, it is genetic. Unless people choose their partners by ordering DNA tests indicating whether their genes have the phenylketonuria mutations, but this is unlikely.

However, this is not so important since, if only one parent has the phenylketonuria gene, the child will not develop the disease, as the dominant gene inherited from the other parent overlaps the recessive phenylketonuria gene.

Common questions

Because it is a rare disease, phenylketonuria is often not on the agenda, which ends up leaving many doubts in people. Know below the most common ones:

I have a child with phenylketonuria and I am pregnant, will the next one also have the disease?

Maybe . If you are with the same partner or your current partner also has one of the phenylketonuria genes, there is a 25% chance that the next child will also have the disease.

When the diet is followed correctly, who has the disease will grow up healthy?

-Yeah . When phenylalanine is within the limits set by the doctor, it will not cause any harm to the individual, which will allow him to grow healthily.

Can my child follow the vaccination schedule normally?

Not only can, but it should. All vaccines should be given normally.

I’ve been on treatment for years and I feel fine, can I suspend the diet?

No . Treatment is for life, and if you feel good now it’s thanks to it.

If I cannot breastfeed, can I give another milk?

No . Milk is one of the foods that should be excluded from the phenylketonuric diet. All of them, whether from cow, goat, buffalo or soy, are rich in protein and should not be given to the child without a doctor’s prescription.

Can someone else breastfeed my child?

No . First because every child must be breastfed by the mother (except in cases prescribed by the doctor) and second that the problem is not the mother’s milk, but the child’s enzymes.

Does my child have the disease because I ate something wrong during pregnancy?

Definitely not ! This is a genetic disease that has nothing to do with what a woman can and cannot eat during pregnancy.

When should I stop breastfeeding?

This varies from case to case. The vast majority can breastfeed until the child’s two years of age. However, it is the nutritionist with the pediatrician who will know how to assess the situation.

Once diagnosed with the disease, the individual must maintain extreme care about food throughout his life. Living with phenylketonuria is not easy, so family support is essential, especially in the person’s formative years, as it is not independent and needs the care of others.

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