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Information about PKU

Understanding PKU and blood Phenylalanine (Phe) management

PKU is an inherited disorder whereby the body fails to break down an amino acid called Phenylalanine (Phe) found in protein-rich food. Without appropriate management, the disorder causes irreversible damage to the developing brain in children. In adults and teenagers, it results in slow reaction times, poor concentration, poor memory and emotional instability leading to depression, anxiety and irritability.

This website provides information about the disorder and how to manage blood Phenylalanine (Phe) levels in everyday life. Select a category from the left of the screen to find out more about PKU management; read a guide to best practices; discover the way ahead and about the genetics.

Confirming a diagnosis: the Guthrie test

The Guthrie or heel prick test is routinely carried out within days of a baby’s birth. A drop of blood is obtained from the baby’s heel and sent to a laboratory for analysis. If Phenylalanine (Phe) levels in the blood are high, your practitioner will arrange further tests to confirm the diagnosis.

The science of PKU: a medical explanation

The body uses amino acids found in food containing protein to build muscle, provide energy and manufacture other chemicals. An enzyme called Phenylalanine Hydroxylase (PAH) and a cofactor or helper called Tetrahydrobiopterin (BH4) breaks down Phenylalanine (Phe) into Tyrosine (Tyr), which is used by the brain to send nerve signals around the body. Tyr is also required to make the skin pigment Melanin and the hormone Thyroxin.

However in people with PKU, the PAH enzyme is deficient and Phe in the blood cannot be broken down. Over time, excess levels of Phe build up in the blood and begin to damage the brain.

As a result, blood Phe levels must be controlled and kept low. Discover more in this section about how to live with the disorder during specific stages of life.

Diagram explaining Phe mechanism in a healthy body and a PKU body

Information for women seeking to become pregnant

Learn about the importance of maintaining low blood Phe levels before and during pregnancy.

Keep up to date with treatment options to help manage blood Phe levels.

Useful tips to help you manage your everyday life.

Tetrahydrobiopterin

See BH4.

Tyrosine (Tyr)

An Amino acid. The Phenylalanine Hydroxylase (PAH) enzyme normally converts phenylalanine (Phe) to Tyr.

Thyroxin

One of two major hormones secreted by the thyroid gland. Its principle function is to stimulate the absorption of oxygen and thereby the metabolism of cells and tissues.

Melanin

Class of compounds which determines the pigmentation of the skin.

Metabolic geneticist

A PKU specialist specialising in inherited metabolic disorders. Each metabolic clinic has at least one of these specialists on staff, whose responsibilities include tracking patient history, interpreting blood tests.

Metabolism/Metabolise

Any chemical process that occurs within the body and is necessary for normal growth and function.

Mild Hyperphenylalaninemia

A condition in which abnormally high levels of Phenylalanine are found in the blood. People with mild Hyperphenylalaninemia have a blood Phe level of <600 μmol/L when not on a Phe-restricted diet.

Mild PKU

A less severe form of Phenylketonuria (PKU) that may still cause mental retardation if not managed with a restricted diet. People with mild PKU have a blood Phe level of 600–1200 μmol/L when not on a Phe-restricted diet and tolerate about 350–400 mg of dietary Phenylalanine a day.

Gene

A portion of Deoxyribonucleic acid (DNA) which holds the information to build and maintain any element of a living organism. When a gene mutates, it may no longer perform the same function, and often the mutation renders it entirely inactive. In the case of Phenylketonuria (PKU), the gene involved in the production of Phenylalanine Hydroxylase is mutated, causing the liver to produce insufficient amounts of that enzyme, and thus restricting the activity of the metabolic pathway that converts Phenylalanine to Tyrosine.

Genetic counsellor

A healthcare professional who specialises in the education and support of patients and families regarding inherited disorders.

Guthrie test

A blood test, also known as the heel prick test performed on newborn infants in the days immediately after birth to detect genetic disorders, including Phenylketonuria (PKU).

Eczema

A skin condition which causes the skin to appear red, swollen and itchy.

Enzyme

A kind of biological molecule that facilitates certain chemical reactions inside the body. People with Phenylketonuria (PKU) lack a certain enzyme called Phenylalanine Hydroxylase (PAH).

Carrier

A person who carries a gene that may cause disorder, but who does not suffer from the disorder itself. A carrier may pass on the defective gene to offspring.

Chorionic villus sampling (CVS)

A prenatal test to determine genetic disorders in the foetus, by sampling a small piece of placenta tissue.

Classic PKU

The most severe form of Phenylketonuria (PKU). People with classic PKU typically have a blood Phenylalanine (Phe) level of >1200 μmol/L when not on a Phe-restricted diet and typically tolerate less than 250–350 mg of dietary Phe a day.

Cofactor

A molecule that combines with an enzyme in order for that enzyme to function. The cofactor of Phenylalanine (Phe) is Tetrahydrobiopterin (BH4).

BH4 (Tetrahydrobiopterin)

An enzyme cofactor that works together with Phenylalanine Hydroxylase to convert Phenylalanine to Tyrosine in the liver. Without the action of both Phenylalanine Hydroxylase and Tetrahydrobiopterin, the chemical process cannot take place, resulting in an accumulation of excess phenylalanine.

BH4 deficiency

A deficiency of the naturally produced BH4 cofactor, caused by mutation in one or more of the enzymes involved in synthesis or regeneration. BH4 deficiency is not the same disorder as Phenylketonuria (PKU).

Amino acid

A type of molecule found inside protein. There are 20 amino acids that are considered standard. Of those, 10 are essential to a healthy diet because the body is unable to produce them. Among the 10 essential amino acids is Phenylalanine.

Amniocentesis

A prenatal test in which cells are collected from the amniotic sac in order to detect chromosomal abnormalities.

Amniotic sac

The thin-walled bag that contains the protective liquid that surrounds the foetus during its development in the womb.

PAH (Phenylalanine Hydroxylase)

An enzyme which works together with Tetrahydrobiopterin (BH4) to convert Phenylalanine (Phe) to Tyrosine (Tyr) in the liver. A deficiency in PAH results in high Phenylalanine levels in the blood, which is the biochemical hallmark of Phenylketonuria (PKU).

Phenotype

An observable characteristic or trait of an organism. Phenotypes result from the expression of an organism’s genes as well as the influence of environmental factors.

phenylalanine (Phe) tolerance

The quantity of Phe a patient may consume without a significant increase in her or his target blood Phe levels. Usually expressed as daily intake.

Phenylalanine (Phe)

A building block of protein, and one of the 10 essential amino acids. An inability to metabolize excess phenylalanine is the characteristic feature of Phenylketonuria (PKU). When the blood concentration of Phenylalanine exceeds what is considered a healthy level, excess amounts may build up in the brain, causing mental retardation.

Phenylalanine Hydroxylase

See PAH.

Phenylketonuria

See PKU.

PKU (Phenylketonuria)

An inherited metabolic defect in protein metabolism. In PKU, the Phenylalanine Hydroxylase (PAH) enzyme is unable to convert Phenylalanine to Tyrosine, resulting in a build-up of Phenylalanine (Phe) in the blood that eventually passes into the brain, causing mental retardation and other neurological problems.

Protein

A type of molecule produced by the body from Amino acids.