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Phenylketonuria - Causes, Symptoms, Diagnosis, Treatment and Prevention

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Phenylketonuria (PKU) is a genetic condition that occurs rarely and causes the buildup of amino acid phenylalanine in the body. Read the article to know more.

Medically reviewed by

Dr. Syed Muneeb Mohammad

Published At April 16, 2022
Reviewed AtMarch 27, 2023

What Is Phenylketonuria?

Amino acids are called the building blocks of protein. Phenylalanine occurs in all proteins and some artificially produced sweeteners. Phenylalanine hydroxylase is an enzyme used by the body to convert phenylalanine into tyrosine. This tyrosine helps the body to create certain neurotransmitters like epinephrine, norepinephrine, and dopamine.

Phenylketonuria is caused due to defects in the gene leading to inadequate or defective formation of phenylalanine hydroxylase. When this enzyme is not present in the body, the breakdown of phenylalanine is affected, and thus, excess accumulation of phenylalanine occurs in the body.

What Are the Symptoms of Phenylketonuria?

The symptoms of this condition can range from mild to severe. Classic PKU (phenylketonuria) is the most severe form of this disorder. An infant suffering from classic PKU can have a normal appearance for the first few months of their life. If the baby is left untreated during this time, the following symptoms can be seen in them:

  1. Seizure attack.

  2. Trembling or shaking or tremors.

  3. Stunted growth.

  4. Hyperactive person.

  5. Conditions affecting the skin like eczema.

  6. Breath, skin, and urine have a different musty odor.

If the early diagnosis is not made in the child at the time of birth and the treatment is not initiated in the early phases, then this disorder can lead to the following symptoms:

  1. Brain damage that is irreversible and can affect intellectual abilities within the first few months of life.

  2. Problems with behavior and seizure attacks in older children.

Variant PKU is a less severe form of PKU and is also called non-PKU hyperphenylalaninemia. This is known to happen when the baby develops excessive phenylalanine in the body. Infants who have such conditions show a milder form of symptoms but may require diet modification to limit the level of phenylalanine in the body. It has been noted that those PKU patients who maintain a proper diet show less or no symptoms, and even the symptoms start to diminish.

How Is Phenylketonuria Caused?

PKU is a condition that can be inherited in a child, and the main cause is known to be a defect in the PAH gene. The PAH gene helps in creating phenylalanine hydroxylase, which is the enzyme responsible for breaking down the phenylalanine in the body. A dangerous level of accumulation of phenylalanine can occur when someone consumes foods rich in high-protein, like eggs and meat.

How Can Phenylketonuria Be Diagnosed?

When you visit your physician, you will be asked questions regarding your previous medical history along with the symptoms you are facing now. Since the 1960s, the method used is a blood test wherein the doctor uses a needle or lancet to withdraw a few drops of blood from the baby’s heel to test for PKU and any other genetic disorders.

The genetic screening and other screening tests are performed when the baby is one to two days old and present in the hospital. Various other tests may be required to confirm the presence of PKU in the baby, and these tests may be performed after six weeks of birth. Further, enzyme testing may be done.

What Are the Treatment Options Available for Phenylketonuria?

As mentioned earlier, diet along with certain medications can help in managing the symptoms of PKU.

1. Diet

The most important thing in the diet is to limit the use of foodstuffs that can lead to an increase in phenylalanine levels. It is suggested to feed infants having PKU with breast milk. Also, they can use certain formula milk like Lofenalac. When the child is at the age of consuming solid foods, it is important to limit the following foods in the child’s diet:

  • Eggs.

  • Fish.

  • Cheese.

  • Nuts.

  • Chicken.

  • Beef.

  • Milk.

  • Beans.

  • Pork.

PKU formula can be given to children to maintain the level of protein required by them. It consists of all the amino acids required by the body except for phenylalanine.

You have to consult your physician to prepare a proper diet plan that will suit your body as each person requires a different type of diet.

2. Medication

The United States Food and Drug Administration (FDA) has recently approved the usage of Sapropterin (Kuvan) for the treatment of PKU. It helps in lowering phenylalanine levels. This medication has to be used along with a special PKU meal plan.

What Is the Relation Between Pregnancy and Phenylketonuria?

A woman suffering from PKU may be at risk of certain complications like miscarriage if they do not follow a certain diet plan during their childbearing years. Also, chances are there that the unborn baby can be exposed to high levels of phenylalanine. This can cause the following complications in the baby:

  • Intellectual disabilities.

  • Low birth weight.

  • Defects in the heart.

  • Growth can be delayed.

  • An abnormally small head.

What Are the Long-Term Effects of Phenylketonuria?

The long-term effect or prognosis is very good if the PKU meal plan is followed properly, closely, and shortly after birth. When there is a delay in diagnosis and treatment, brain damage can occur. This can ultimately cause intellectual disabilities during the child’s first year of life itself.

Is It Possible to Prevent Phenylketonuria?

PKU is a genetic condition; it is difficult to prevent it. An enzyme assay can be done for couples who are planning to have children. This test may also be carried out during pregnancy to screen for PKU in unborn babies.


PKU is a rare condition but can affect the overall health of the individual and hence requires early diagnosis and management. Online medical platforms have made consultations with physicians and specialists easy. Hence, consult a specialist to know more about the condition.

Frequently Asked Questions


Which Gene Is Mutated in Phenylketonuria?

Phenylketonuria is a genetic disorder characterized by the build-up of an amino acid called phenylalanine. The condition occurs when there is a defect in the gene responsible for the breakdown of phenylalanine. For example, phenylketonuria or PKU is caused due to the mutations in the PAH gene, responsible for producing an enzyme called phenylalanine hydroxylase. This enzyme is essential for processing phenylalanine; lack of which leads to the accumulation of phenylalanine in the body.


How Do Children Inherit Phenylketonuria?

Phenylketonuria is a genetic condition that occurs due to the mutation in the PAH gene. PKU is transmitted from parents to their offspring in an autosomal recessive inheritance pattern. This means that each cell has two copies of the mutated gene, receiving one copy from each parent. Therefore, the affected child's parents carry one copy of the defective gene and do not show any disease symptoms. However, when this gene is passed down to the child, two copies of the defective gene result in phenylketonuria manifestation.


What Type of Gene Mutation Occurs in Phenylketonuria?

Phenylketonuria occurs due to mutations in the PAH gene. The type of mutation observed is the deletion of the single base pair of the PAH gene, leading to a stop signal during the enzyme synthesis. Additionally, these deletions also lead to missense (single nucleotide change) or nonsense mutations (point mutations), resulting in the occurrence of phenylketonuria.


Is Phenylketonuria a Monogenic or Polygenic Trait?

Monogenic mutations lead to conditions caused due to the mutations in a single gene. In contrast, polygenic genetic disorders occur due to defects in one or more genes. Phenylketonuria is categorized as a monogenic trait with an autosomal recessive type of inheritance. Mutations in the PAH gene are responsible for the defective function of the enzyme phenylalanine hydroxylase leading to metabolic and mental changes in the affected person.


Is Phenylketonuria a Chromosomal Disorder?

Yes, phenylketonuria is a classic chromosomal disorder. It follows an autosomal recessive pattern where both copies of the defective gene are inherited from each parent. As a result, the mutation occurs in the PAH gene located on chromosome 12. The condition results in the accumulation of phenylalanine in the tissues due to the lack of phenylalanine hydroxylase enzyme.


How is the body affected by phenylketonuria?

If phenylketonuria is not identified and treated, it can adversely affect the body. The symptoms occur due to an abnormal build-up of phenylalanine in the body. The effects of this accumulation lead to the following symptoms:
- Eczema of the skin.
- Reduced intellectual abilities.
- Psychologic disorders.
- Emotional and behavior issues.
- Small head circumference or microcephaly.
Fair skin.
- Blue eyes.
- Developmental delays.
- Seizures.
- Musty smell from breath, urine, and skin.
- Hyperactivity.


Does Phenylketonuria Result From a Dominant or Recessive Type of Inheritance?

Phenylketonuria is a genetic disorder that follows an autosomal recessive pattern of inheritance. Mutations occur in the PAH gene resulting in a deficiency of the enzyme phenylalanine hydroxylase. Autosomal recessive inheritance is characterized by inheriting a copy of the mutated gene from each patient. Therefore, the affected individual carries two copies of the defective gene.


Which Enzyme Deficiency Causes Phenylketonuria?

Phenylalanine is an amino acid that gets converted to tyrosine under the action of the enzyme phenylalanine hydroxylase. PAH gene mutations result in the reduction or deficiency of the enzyme phenylalanine hydroxylase. As a result, phenylalanine (consumed from diet) is not effectively processed, leading to its accumulation in the tissues.


What Are the Common Symptoms of Phenylketonuria?

The common presenting symptoms of phenylketonuria include:
- Skin eczema.
- Small head circumference (microcephaly).
- Defects in the heart.
- Intellectual disabilities.
- Musty smell from urine, skin, and breath.
- Tremors, shaking, and seizures.
- Psychologic disturbances.
- Growth retardation.
- Lighter skin and hair color.


When Do Phenylketonuria Symptoms Appear?

Babies affected with phenylketonuria do not instantly develop symptoms of the disease. Instead, symptoms of phenylketonuria appear a few months after the baby is born. Infants lead a normal life during the initial months and show signs of phenylketonuria around six months after birth. The symptoms also depend on the severity of the condition.


Does Phenylketonuria Develop Later in Life?

Phenylketonuria commonly affects infants and young children. However, in rare cases, phenylketonuria can affect adults in the later stages. In addition, cases of phenylketonuria have been reported in adults, and the condition resembles other neurological diseases. Additionally, instances of undiagnosed phenylketonuria might get diagnosed in later stages of life.


What Is the Test for Phenylketonuria?

Babies are screened for phenylketonuria within 24 hours after their birth. A blood sample is taken from the baby to assess the quantity of phenylalanine in the blood. Usually, phenylalanine should be less than 2 mg/dL. It is considered abnormal if the amount is more than 4 mg/dL. However, abnormal levels of phenylalanine do not confirm the diagnosis of phenylketonuria. Chances of false-positive results (if the baby is born prematurely) and false negative (if the babies are not eating) are possible.


How Commonly Does Phenylketonuria Occur?

Phenylketonuria is a rare genetic disorder, and its occurrence varies depending on ethnicity and geographic location. However, it is estimated to affect one in 10,000 to 15,000 live births in the United States alone every year. Fortunately, babies are screened for phenylketonuria after birth, and the treatment is initiated. Therefore, most of the affected infants do not develop a severe form of the condition.


What Is the Dietary Recommendation for Phenylketonuria?

Infants affected with phenylketonuria are advised to follow a diet to avoid the accumulation of phenylalanine. The recommended regime mainly includes a low-protein diet. Foods containing eggs, meat, dairy products, etc., should be avoided. Instead, carbohydrates such as potatoes, rice, and cereals can be consumed. Additionally, it is necessary to ensure that the babies get the amino acid supplements required for normal development. People affected by PKU should also avoid foods rich in aspartame. Sugar substitutes, artificial sweeteners, chewing gums, fizzy drinks, etc., contain aspartame and hence should be avoided.


What Are the Consequences of Untreated Phenylketonuria?

It is necessary to diagnose and treat phenylketonuria as early as possible. Untreated cases can lead to the accumulation of abnormal levels of phenylalanine in the body. In addition, PKU can affect the unborn fetus if mothers develop phenylketonuria during pregnancy. The complications associated with untreated phenylketonuria include:
- Permanent intellectual disability.
- Irreversible cerebral damage.
- Seizures, tremors, and shaking.
- Behavioral, emotional, and intellectual issues.
- Developmental retardation.
- Skin conditions such as eczema.
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Dr. Syed Muneeb Mohammad
Dr. Syed Muneeb Mohammad

Pediatric Allergy/Asthma Specialist


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