Glossary

PKU glossary – Information and resource for PKU research

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.

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).

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).

Deoxyribonucleic acid (DNA): DNA makes up chromosomes, which pass on the hereditary properties of all living organisms.
Dietitian/Nutritionist: A medical expert whose focus is diet and nutrition, and one of the key players in an individual’s management of Phenylketonuria (PKU). A metabolic clinic is typically run by a staff of registered dietitians/nutritionists overseen by a few metabolic geneticists and/or physicians. The registered dietitians/nutritionists are responsible for tracking the nutritional needs of PKU patients and recommending dietary changes when appropriate

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).

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).

Hyperphenylalaninemia: A condition in which abnormally high levels of Phenylalanine are found in the blood. This is a sign of Phenylketonuria (PKU), but it can also be found in several other conditions. The newborn screening test is technically a test for Hyperphenylalaninemia rather than for PKU. In other words, if a newborn tests positive in the first screening, all it means is that the newborn has a high level of Phenylalanine (Phe) in his or her blood, which may or may not be due to PKU. This means additional testing is required to learn what is causing Hyperphenylalaninemia.

Inborn error of metabolism: A category of disorders affecting metabolism, which are inherited through genes and originate at birth. Phenylketonuria (PKU) is an example of an inborn error of metabolism.
In vitro fertilization (IVF): A process by which egg cells are fertilised by sperm outside the womb to assist pregnancy.

Large neutral amino acids (LNAA):: Large neutral amino acids (LNAA) may also be used in therapy for PKU. LNAA, taken in tablet form, compete with Phe for transport across the blood-brain barrier, reducing the concentration of Phe in the blood.

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.

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.

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.