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Genetic and Rare Diseases Information Center (GARD)

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Tetrahydrobiopterin deficiency

Other Names for this Disease
  • BH4 deficiency
  • Hyperphenylalaninemia caused by a defect in biopterin metabolism
  • Hyperphenylalaninemia, non-phenylketonuric
  • Non-phenylketonuric hyperphenylalaninemia
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What is tetrahydrobiopterin deficiency?

What are the signs and symptoms of tetrahydrobiopterin deficiency?

What is tetrahydrobiopterin deficiency?

Tetrahydrobiopterin (BH4) deficiency is a neurological condition caused by an inborn error of metabolism. BH4 is a substance in the body that enhances the action of other enzymes. Deficiency of BH4 leads to abnormally high blood levels of the amino acid phenylalanine, and low levels of certain neurotransmitters.[1] Signs and symptoms can range from very mild to severe.[2] Affected newborns appear normal at birth, but may begin to experience neurological symptoms such as abnormal muscle tone; poor sucking and coordination; seizures; and delayed motor development. Without early, appropriate treatment, the condition can cause permanent intellectual disability and even death.[1] BH4 deficiency is caused by mutations in any one of several genes including the GCH1, PCBD1, PTS, and QDPR genes. It is inherited in an autosomal recessive manner.[3]Treatment depends on the genetic cause and severity, and may include a low phenylalanine diet; oral BH4 supplementation; and neurotransmitter replacement.[1]
Last updated: 11/2/2012

What are the signs and symptoms of tetrahydrobiopterin deficiency?

Infants with tetrahydrobiopterin (BH4) deficiency typically appear normal and healthy at birth.[1][2] Neurological signs and symptoms usually become apparent over time, and can range from mild to severe.[3][2] These may include abnormal muscle tone; poor sucking and coordination; seizures; and delayed motor development.[1] Other manifestations may include decreased spontaneous movements and difficulty swallowing.[3][2]

Without early and appropriate treatment, signs and symptoms progress and affected individuals may experience irreversible intellectual disability, behavioral problems, an inability to control body temperature, and even death in severe cases.[3][1]
Last updated: 11/2/2012

  1. Tetrahydrobiopterin Deficiency. NORD. May 23, 2008; Accessed 10/31/2012.
  2. Noah S Scheinfeld. Tetrahydrobiopterin Deficiency. Medscape Reference. June 27, 2012; Accessed 11/2/2012.
  3. Tetrahydrobiopterin deficiency. Genetics Home Reference. July 2011; Accessed 11/2/2012.