Article: Hyperphenylalaninemia

What is hyperphenylalaninemia?

Hyperphenylalaninemia is a disorder characterized by increased amounts of the amino acid phenylalanine in the bloodstream. (Amino acids are the building blocks of proteins.) Excess phenylalanine is toxic to nerve cells and, if left untreated, can result in brain damage.

Genetic changes are related to the following types of hyperphenylalaninemia.

• phenylketonuria
• tetrahydrobiopterin deficiency

High levels of phenylalanine interfere with the function of nerve cells and can prevent normal brain development. Resulting signs and symptoms range from mild to severe and can include mental retardation, seizures, and behavioral problems. For more specific information, refer to the summaries for phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency.

How common is hyperphenylalaninemia?

PKU is the most common type of hyperphenylalaninemia, with 1 in 10,000 to 25,000 affected infants born in the United States each year. BH4 deficiency is a much rarer cause of increased phenylalanine levels.

What genes are related to hyperphenylalaninemia?

Mutations in the GCH1, PAH, PCBD1, PTS, and QDPR genes cause hyperphenylalaninemia.

In about 98 percent of cases, increased phenylalanine levels are a result of reduced or absent activity of an enzyme called phenylalanine hydroxylase. Made by the PAH gene, this enzyme converts phenylalanine into other critical molecules in the body. If the enzyme functions incorrectly because of a gene mutation, phenylalanine builds up in the bloodstream. Hyperphenylalaninemia caused by a lack of phenylalanine hydroxylase is called phenylketonuria or PKU.

The other 1 to 2 percent of cases of hyperphenylalaninemia are caused by reduced levels of other enzymes in the same chemical pathway as phenylalanine hydroxylase. These enzymes are made by several genes, including GCH1, PTS, QDPR, and PCBD. Hyperphenylalaninemia caused by mutations in any of these genes is known as BH4 deficiency or hyperphenylalaninemia caused by a defect in biopterin metabolism.

In premature infants, a defect in processing the amino acid tyrosine is a common cause of hyperphenylalaninemia. This increase is usually temporary.

How do people inherit hyperphenylalaninemia?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.