Tetrahydrobiopterin deficiency (also known as BH4 deficiency) is a rare disorder that increases the blood levels of a substance called phenylalanine. Phenylalanine is an amino acid obtained through the diet. It is found in all proteins and in some artificial sweeteners. If tetrahydrobiopterin deficiency is not treated, excess phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious health problems. The alpha-amino acid Phenylalanine exists in two forms, the D- and L- forms, which are enantiomers (mirror-image molecules) of each other. ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... A sweetener is a food additive which adds the basic taste of sweetness to a food. ... Tetrahydrobiopterin Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. ...

High levels of phenylalanine are present from infancy in people with untreated tetrahydrobiopterin deficiency. The resulting signs and symptoms range from mild to severe. Mild complications may include temporary low muscle tone. Severe complications include mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature. Mental retardation (also called mental handicap and, as defined by the UK Mental Health Act 1983, mental impairment and severe mental impairment) is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal global intellectual capacity as... Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when temperature surrounding is very different. ...

Epidemiology

This condition is very rare; approximately 450 cases have been reported worldwide. In most parts of the world, only 1 % to 2 % of all infants with high phenylalanine levels have this disorder. In China, about 30 % of newborns with elevated levels of phenylalanine have a deficiency of tetrahydrobiopterin.^[1]

Related genes

Mutations in the GCH1, PCBD1, PTS and QDPR genes cause tetrahydrobiopterin deficiency. QDPR (quinoid dihydropteridine reductase) is a human gene that produces the enzyme quinoid dihydropteridine reductase. ...

Tetrahydrobiopterin is a compound that helps convert several amino acids, including phenylalanine, to other essential molecules in the body. It is also involved in the production of chemicals called neurotransmitters that transmit signals between nerve cells in the brain. Tetrahydrobiopterin deficiency can be caused by mutations in one of several genes, including GCH1, PCBD1, PTS, and QDPR. These genes make enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. Tetrahydrobiopterin deficiency also disrupts the levels of certain neurotransmitters in the brain, which affects the function of the central nervous system. In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell. ... In biology, mutations are changes to the genetic material (usually DNA or RNA). ... Comparative brain sizes In animals, the brain, or encephalon (Greek for in the head), is the control center of the central nervous system. ... A diagram showing the CNS: 1. ...

Genetics

This condition is inherited in an autosomal recessive pattern, which means two copies of a specific 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. In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ...

Treatment

Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan) and supplements of folinic acid in DHPR deficiency.^[2] Folinic acid (INN) or leucovorin (USAN), generally administered as calcium folinate (or leucovorin calcium), is an adjuvant used in cancer chemotherapy involving the drug methotrexate. ...

See also

• Phenylketonuria
• Tetrahydrobiopterin

Phenylketonuria [PKU] is a human genetic disorder (though it is possible to exist in mice), in which the body lacks phenylalanine hydroxylase, the enzyme necessary to metabolize phenylalanine to tyrosine. ... Tetrahydrobiopterin Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. ...

References

• ↑  Liu TT, Chiang SH, Wu SJ, Hsiao KJ (2001). "Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese". Clin Chim Acta 313 (1-2): 157-69. PMID 11694255.
• Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L (2004). "Dihydropteridine reductase deficiency in man: from biology to treatment". Med Res Rev 24 (2): 127-50. PMID 14705166.
• ↑  Shintaku H (2002). "Disorders of tetrahydrobiopterin metabolism and their treatment". Curr Drug Metab 3 (2): 123-31. PMID 12003346.

External links

• The Tetrahydrobiopterin website