Phenylketonuria (PKU) is a rare, inherited metabolic disorder that is characterized by the inability of the body to utilize the essential amino acid, phenylalanine (Phe). Amino acids, usually obtained from the food we eat, are the building blocks for body proteins. PKU is caused by a deficiency of the liver produced enzyme phenylalanine hydroxylase (PAH).

This enzyme normally converts Phe to another amino acid, tyrosine. Without this enzyme, Phe accumulates in the blood and body tissues. Excess Phe is toxic to the central nervous system and causes the severe problems normally associated with PKU. When left untreated, PKU patients who consume too much Phe are at risk of severe neurological complications, including IQ loss, memory loss, concentration problems, mood disorders, and in some cases, severe mental retardation.

Damage done is irreversible so early detection is crucial. When treatment is begun early (within the first few weeks of life) and rigorously adhered to, affected children can expect normal development and a normal life span. PKU can be treated by a diet low in phenylalanine and high in tyrosine. While there is no cure, in recent years a few drug products have become available that can be used in limited cases to mitigate the effects of the disorder. Other therapies currently under investigation include an injectable form of PAH and gene therapy.


- Classical PKU (PKU), where the dietary tolerance to Phe is less than 350-400 mg per day and then residual activity of PAH is less than 5%. This is the most common form

- Moderate or Mild PKU (PKU), where the dietary tolerance to Phe is less than 350-600 mg per day and then residual activity of PAH is less than 10%.

- Benign PKU (PKU), where there are no dietary restrictions of Phe but the residual activity of PAH is less than 5%


The most severe form of this disorder is known as classic PKU.

- Infants with classic PKU appear normal until they are a few months old.

- Without treatment with a special low-phenylalanine diet, these children develop permanent intellectual disability.

- Seizures, delayed development, behavioral problems, and psychiatric disorders are also common.

- Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body, lighter skin & hair than unaffected family members and are more likely to have skin disorders such as eczema.

Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet.

- Babies born to mothers with PKU and uncontrolled phenylalanine levels (women who no longer follow a low-phenylalanine diet) have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth.

- These infants may also have a low birth weight and grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems.

- Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss


Mutations in the PAH gene cause phenylketonuria.

The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme converts the amino acid phenylalanine to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet is not processed effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.

Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious medical problems. Mutations in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition, such as variant PKU or non-PKU hyperphenylalaninemia.

Changes in other genes may influence the severity of PKU, but little is known about these additional genetic factors.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.


Newborn screening allows early identification and early implementation of treatment. The goal of PKU treatment is to maintain the blood level of Phe between 2 and 10 mg/dl[9]. Some Phe is needed for normal growth. This requires a diet that has some Phe but in much lower amounts than normal. High protein foods such as: meat, fish, poultry, eggs, cheese, milk, dried beans, and peas are avoided. Instead, measured amounts of cereals, starches, fruits, and vegetables, along with a milk substitute are usually recommended. These foods are allowed in quantities that suit the individual child's tolerance for Phe; some can have fairly liberal diets and still maintain good control of blood phe, while others must have a very strict diet. A synthetic, Phe free formula is used as a nutritional substitute for the eliminated foods. Formulas are available for all age groups.

Previously, PKU affected individuals were allowed to go off diet after approximately 6 to 12 years of age. Most authorities now recommend lifelong dietary restriction of Phe for individuals with classic PKU, in order to promote maximal development and cognitive abilities. Trying to reinstitute the PKU diet after a period of 'relaxation' to a regular diet, has been difficult for many individuals. Periodic Phe blood level measurement, and the guidance of a nutritionist and other members of the health care team, allow individuals and families to work toward consistently maintaining the blood level in the desirable range.

In just the past few years two new products have become available for persons with PKU. Kuvan, a prescription drug, causes residual enzyme activity to work harder to reduce blood Phe levels and has been effective in reducing blook Phe levels in some people with PKU. Another new product with limited application are large neutral amino acides (LNAA's) which work by blocking Phe uptake through the digestive tract.






*DISCLAIMER: The information listed on the PKU Helping Hands, Inc. website is for educational and informational use only. This information is not intended, nor should be used as professional advice. In the event that you need to seek medical advice, please contact your clinic.