Tetrahydrobiopterin deficiency

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.

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.

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.

Read more about the GCH1, PCBD1, PTS, and QDPR genes.

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.

Where can I find information about treatment for tetrahydrobiopterin deficiency?
These resources address the management of tetrahydrobiopterin deficiency and may include treatment providers.

MedlinePlus Encyclopedia: Serum Phenylalanine Screening
You might also find information on treatment of tetrahydrobiopterin deficiency in Educational resources and Patient support.

Where can I find additional information about tetrahydrobiopterin deficiency?
You may find the following resources about tetrahydrobiopterin deficiency helpful. These materials are written for the general public.

MedlinePlus - Health information (2 links)
Educational resources - Information pages (5 links)
Patient support - For patients and families (3 links)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Tests - DNA tests ordered by healthcare professionals (4 links)
ACTion Sheets - Newborn screening follow up (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
Online Books - Medical and science texts
Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Disorders of Tetrahydrobiopterin and Related Biogenic Amines
OMIM - Genetic disorder catalog (4 links)
What other names do people use for tetrahydrobiopterin deficiency?
BH4 Deficiency
Hyperphenylalaninemia caused by a defect in biopterin metabolism
Hyperphenylalaninemia, Non-Phenylketonuric
Non-Phenylketonuric Hyperphenylalaninemia
See How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about tetrahydrobiopterin deficiency?
See How can I find a genetics professional in my area? in the Handbook.
Ask the Genetic and Rare Diseases Information Center.
Submit your question to Ask the Geneticist.
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.

What does it mean if a disorder seems to run in my family?
What are the different ways in which a genetic condition can be inherited?
If a genetic disorder runs in my family, what are the chances that my children will have the condition?
Why are some genetic conditions more common in particular ethnic groups?
These links provide additional genetics resources that may be useful.

Genetics and health
Resources for Patients and Families
Resources for Health Professionals
What glossary definitions help with understanding tetrahydrobiopterin deficiency?
acids ; amino acid ; atypical ; autosomal ; autosomal