What is tetrahydrobiopterin deficiency?
Tetrahydrobiopterin deficiency is a rare disorder that increases the levels of several substances, including phenylalanine, in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If tetrahydrobiopterin deficiency is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.
What are the symptoms of tetrahydrobiopterin deficiency?
High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. Infants with this condition appear normal at birth, but medical problems ranging from mild to severe become apparent over time.
The signs and symptoms of this condition can include:
- intellectual disability,
- progressive problems
with development, - movement disorders,
- difficulty swallowing,
- seizures,
- behavioral problems, and
- an inability to control body temperature.
Tetrahydrobiopterin Deficiency Symptoms & Signs
Tetrahydrobiopterin deficiency is a very rare disorder that increases the levels of several substances, including phenylalanine, in the blood. Most cases of elevated levels of phenylalanine in the blood are caused by a different condition known as phenylketonuria. Tetrahydrobiopterin is a molecule that helps process several amino acids in the body, including phenylalanine.
Signs and symptoms of tetrahydrobiopterin deficiency include
- intellectual disability,
- progressive problems with development,
- movement disorders,
- difficulty swallowing,
- seizures, and
- behavioral problems.
Learn more about tetrahydrobiopterin deficiency »
How common is tetrahydrobiopterin deficiency?
This condition is very rare, affecting about 1 per
million newborns. In most parts of the world, tetrahydrobiopterin deficiency
accounts for only 1 percent to 2 percent of all cases of elevated phenylalanine
levels. The remaining cases are caused by a similar condition called
phenylketonuria (PKU). In certain countries, including Saudi Arabia, Taiwan, China, and Turkey, it is more common for elevated levels of phenylalanine to be caused by tetrahydrobiopterin deficiency.
What genes are related to tetrahydrobiopterin deficiency?
Tetrahydrobiopterin deficiency can be caused by mutations in one of several genes, including GCH1, PCBD1, PTS, and QDPR. These genes provide instructions for making enzymes that help produce and recycle tetrahydrobiopterin in the body. Tetrahydrobiopterin (also known as BH4) is a molecule that helps process several amino acids, including phenylalanine. It is also involved in the production of
chemicals called neurotransmitters, which transmit signals between nerve cells
in the brain.
If one of the enzymes fails to function correctly because
of a gene mutation, little or no tetrahydrobiopterin is available to help
process phenylalanine. As a result, phenylalanine can build up 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. Tetrahydrobiopterin deficiency can also alter the levels of certain neurotransmitters, which disrupts normal brain function.
How do people inherit tetrahydrobiopterin deficiency?
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.
What other names do people use for tetrahydrobiopterin deficiency?
- HPA
- BH4 Deficiency
- Hyperphenylalaninemia caused by a defect in biopterin
metabolism - Hyperphenylalaninemia, Non-Phenylketonuric
- Non-Phenylketonuric Hyperphenylalaninemia
Source: Genetics Home Reference, National Library of
Medicine, National Institutes of Health