Phenylketonuria or PKU is caused by lack of an enzyme called phenylalanine hydroxylase. The enzyme converts the amino acid phenylalanine into another amino acid called tyrosine.

Being deficient in phenylalanine hydroxylase is caused by genetic inheritance of a faulty gene that codes for the enzyme.

When the body is deficient in phenylalanine hydroxylase, the amino acid phenylalanine may build up in the body.

Concentrations of the amino acid rise in blood and it gets deposited in the tissues especially in brain.

This may sometimes lead to severe brain damage, mental retardation etc.

PKU affects one in 10,000 newborns.

Symptoms range widely among sufferers and the condition may be detected at routine screening tests at birth without the baby manifesting any symptoms. (1)

Classic Symptoms of PKU

The classic symptoms of PKU are (1, 2) –

• Skin and hair color

  Phenylalanine is important in production of the chemical melanin in the body.

  Melanin is responsible for the color of skin and hair. Babies born with PKU are often more light skinned, light haired and light eyed than their siblings or parents who do not have the disease.

• When the disease has progressed beyond early developmental stage without detection, there may be delayed mental and social developments.
• Microcephaly or small head size
• Increased activity in the child or behavioural problems
• Mental retardation and developmental delays
• Jerky movements of the legs and arms
• Tremors
• Abnormal movements of the hands and arms
• Seizures or epilepsy like features
• Skin rashes and eczema
• “Musty” or “mousy” odor from the breath, urine and skin. This is due to unusual build up of the amino acid phenylalanine in the body.
• There are low levels of myelin formation. Myelin forms coats of protection over the nerves. Brain chemicals like dopamine, norepinephrine, and serotonin productions are also reduced. On clinical examination there may be exaggerated deep tendon reflexes and sometimes paralysis of all four or any two limbs.
• Patients with PKU are advised to consume low protein diets. However, vitamin B₁₂ is found in natural animal proteins. Thus, when a low protein diet is taken, patients may be at risk of vitamin B₁₂ deficiency.

Types of PKU

There are few basic types of PKU (4) –

• Phenylketonuria (PKU) or classic PKU that is most severe if untreated.

  There is near complete deficiency of phenylalanine hydroxylase.

  Here the plasma levels of Phenylalanine may be greater than 1000 µmol/L. Patient may be able to take in not more than 250-300 mg of phenylalanine per day.

  These patients are at the highest risk of developing mental retardations and cognitive delays.

• Moderate PKU occurs in individuals who can take in 350-400 mg of dietary phenylalanine per day. Those with Mild PKU tolerate 400-600 mg of dietary phenylalanine per day.
• Mild hyperphenylalaninemia (MHP) – In these patients there may be a high Phenylalanine concentration of over 120 µmol/L but less than 600 µmol/L on normal diet. These patients have a low risk of cognitive impairments if no dietary interventions are started.

Babies with PKU

Babies with classic PKU or severe PKU may be normal in appearance for the initial few months of their lives.

However, if they are not treated or if their diets are not regulated for phenylalanine they may go on to show developmental delays and mental retardation.

Those born with less severe forms of PKU may have milder degrees of mental retardation if their diets are not regulated and phenylalanine is not restricted.

Babies with very slight degree of PKU called hyperphenylalaninemia, may have no apparent symptoms and may not need dietary interventions. (3)

Further Reading

• All Phenylketonuria Content
• What is Phenylketonuria (PKU)?
• PKU Causes
• PKU Diagnosis
• PKU Treatment

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.