Tetrahydrobiopterin deficiency 3407595 216176372 2008-05-31T12:39:33Z 58.172.238.101 {{Infobox_Disease | Name = {{PAGENAME}} | Image = Tetrahydrobiopterin1.png | Caption = [[Tetrahydrobiopterin]] | DiseasesDB = | ICD10 = {{ICD10|E|70|1|e|70}} | ICD9 = {{ICD9|270.1}} | OMIM = | MedlinePlus = | eMedicineSubj = ped| eMedicineTopic = 2226| MeshID = | }} '''Tetrahydrobiopterin deficiency''' (also known as '''BH4 deficiency''') is a rare disorder that increases the blood levels of [[phenylalanine]]. Phenylalanine is an [[amino acid]] obtained through the diet. It is found in all proteins and in some [[artificial sweetener]]s. 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. 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]]. Patients may have a high frequency red hair within the population. Most commonly associated with 6-pyruvoyl-tetrahydropterin synthase deficiency It was first characterized in 1975.<ref>{{cite journal | author=Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L | title=Dihydropteridine reductase deficiency in man: from biology to treatment | journal=Med Res Rev | year=2004 | pages=127–50 | volume=24 | issue=2 | pmid=14705166 | doi=10.1002/med.10055}}</ref> ==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 [[Taiwan]], about 30 % of newborns with elevated levels of phenylalanine have a deficiency of tetrahydrobiopterin.<ref>{{cite journal | author=Liu TT, Chiang SH, Wu SJ, Hsiao KJ | title=Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese | journal=Clin Chim Acta | year=2001 | pages=157–69 | volume=313 | issue=1-2 | pmid=11694255 | doi=10.1016/S0009-8981(01)00669-6}}</ref> ==Related genes== Mutations in the [[GCH1]], [[PCBD1]], [[PTS]] and [[QDPR]] genes cause tetrahydrobiopterin deficiency. Tetrahydrobiopterin is a compound that helps convert several [[amino acid]]s, including phenylalanine, to other essential molecules in the body. It is also involved in the production of chemicals called [[neurotransmitter]]s that transmit signals between nerve cells in the brain. Tetrahydrobiopterin deficiency can be caused by [[mutation]]s 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]]. ==Genetics== [[Image:autorecessive.jpg|thumb|right|Tetrahydrobiopterin deficiency has an [[autosomal recessive]] pattern of inheritance.]] This condition is inherited in an [[autosomal recessive]] pattern, which means two copies of a specific gene in each cell are altered in order for the individual to be afflicted. 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. ==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 precursors (L-dopa/CarbiDOPA and 5-hydroxytryptophan) and supplements of [[folinic acid]] in DHPR deficiency.<ref>{{cite journal | author=Shintaku H | title=Disorders of tetrahydrobiopterin metabolism and their treatment | journal=Curr Drug Metab | year=2002 | pages=123–31 | volume=3 | issue=2 | pmid=12003346 | doi=10.2174/1389200024605145}}</ref> ==See also== * [[Phenylketonuria]] * [[Tetrahydrobiopterin]] <br />For a thorough scientific overview of disorders of tetrahydrobiopterin and related biogenic amines, one can consult chapter 78 of OMMBID<ref> [[Charles Scriver]], Beaudet, A.L., Valle, D., Sly, W.S., Vogelstein, B., Childs, B., Kinzler, K.W. (Accessed 2007). [http://www.ommbid.com The Online Metabolic and Molecular Bases of Inherited Disease]. New York: McGraw-Hill. - Summaries of 255 chapters, full text through many universities. There is also the [http://books.mcgraw-hill.com/medical/ommbid/blog/ OMMBID blog]. </ref>. For more online resources and references, see [[inborn errors of metabolism]]. == References == {{reflist}} ==External links== * [http://www.bh4.org/ The Tetrahydrobiopterin website] {{Amino acid metabolic pathology}} [[Category:Genetic disorders]] [[Category:Autosomal recessive disorders]] [[Category:Inborn errors of metabolism]]