MCID: TTR005
MIFTS: 46

Tetrahydrobiopterin Deficiency malady

Metabolic category

Summaries for Tetrahydrobiopterin Deficiency

Sources:
21Genetics Home Reference, 43NIH Rare Diseases, 64Wikipedia, 33MalaCards
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NIH Rare Diseases:43 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. signs and symptoms can range from very mild to severe. 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. 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.treatment depends on the genetic cause and severity, and may include a low phenylalanine diet; oral bh4 supplementation; and neurotransmitter replacement. last updated: 11/2/2012

MalaCards: Tetrahydrobiopterin Deficiency, also known as hyperphenylalaninemia, non-phenylketonuric, is related to hyperphenylalaninemia and phenylketonuria. An important gene associated with Tetrahydrobiopterin Deficiency is PTS (6-pyruvoyltetrahydropterin synthase), and among its related pathways are tyrosine biosynthesis IV and Tyrosine metabolism p.1 (dopamine) . The compounds estrogen and 7-biopterin have been mentioned in the context of this disorder. Affiliated tissues include brain, t cells and endothelial, and related mouse phenotypes are endocrine/exocrine gland and pigmentation.

Genetics Home Reference:21 Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.

Wikipedia:64 Tetrahydrobiopterin deficiency (THBD, BH4D), also called THB or BH4 deficiency, is a rare metabolic... more...

Aliases & Classifications for Tetrahydrobiopterin Deficiency

Sources:
64Wikipedia, 43NIH Rare Diseases, 21Genetics Home Reference, 61UMLS
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Metabolic


Aliases & Descriptions:

tetrahydrobiopterin deficiency 64 43 21
hyperphenylalaninemia, non-phenylketonuric 43 21 61
non-phenylketonuric hyperphenylalaninemia 64 43 21
bh4 deficiency 64 43 21
hyperphenylalaninemia caused by a defect in biopterin metabolism 43 21


Related Diseases for Tetrahydrobiopterin Deficiency

Sources:
17GeneCards, 18GeneDecks
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Diseases related to Tetrahydrobiopterin Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 112)
idRelated DiseaseScoreTop Affiliating Genes
1hyperphenylalaninemia30.7GCH1, QDPR, PCBD1, TPH1, SPR, PTS
2phenylketonuria30.4PTS, PAH, QDPR
3gtp cyclohydrolase i deficiency30.3GCH1, QDPR, TH, PTS
4hyperprolactinemia30.0GH1, PRL, TH
5atherosclerosis30.0SOD1, NOS3, NOS1, PTS
6hyperphenylalaninemia, bh4-deficient, a10.3
7t cell deficiency10.2
8rabies10.1
9gastroparesis10.1
10hyperphenylalaninemia due to dehydratase deficiency10.1
11dihydropteridine reductase deficiency10.1
126-pyruvoyl-tetrahydropterin synthase deficiency10.1
13sepiapterin reductase deficiency10.1
14hypoxia10.1
15cerebral palsy10.0GCH1
16migraine10.0TPH1
17panic disorder10.0TPH1
18autoimmune polyendocrine syndrome10.0TPH1
19borderline personality disorder10.0TPH1
20arthritis10.0HPRT1
21neuroblastoma10.0TH
22obsessive-compulsive disorder10.0TPH1
23tyrosine hydroxylase deficiency10.0TH
24acquired immunodeficiency syndrome10.0DHFR
25spina bifida10.0DHFR
26cystic fibrosis10.0PAH
27rett syndrome10.0TH
28irritable bowel syndrome10.0TPH1
29tuberculosis10.0DHFR
30down syndrome10.0SOD1
31glucose intolerance10.0GH1
32pancreatitis10.0SOD1
33multiple system atrophy10.0TH
34stomach cancer10.0PTS
35dwarfism10.0GH1
36toxic encephalopathy10.0TH
37intellectual disability10.0HPRT1, PAH
38tyrosinemia10.0PAH, PTS
39pheochromocytoma10.0TH, GCH1
40colorectal cancer10.0PTS, DHFR
41motor neuron disease10.0SOD1
42myopathy10.0NOS1, QDPR
43acute myocardial infarction10.0NOS1
44malaria10.0DHFR, HPRT1
45addison's disease10.0TH, TPH1
46xeroderma pigmentosum10.0HPRT1, DHFR
47hepatopulmonary syndrome10.0NOS3
48liver cirrhosis10.0NOS3
49dementia10.0NOS1, TH
50varicocele10.0PRL

Graphical network of the top 20 diseases related to Tetrahydrobiopterin Deficiency:



Diseases related to tetrahydrobiopterin deficiency

Clinical Features for Tetrahydrobiopterin Deficiency

Drugs & Therapeutics for Tetrahydrobiopterin Deficiency

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials
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Approved drugs:

Search CenterWatch for Tetrahydrobiopterin Deficiency

Drug clinical trials:

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Search NIH Clinical Center for Tetrahydrobiopterin Deficiency

Search CenterWatch for Tetrahydrobiopterin Deficiency

Genetic Tests for Tetrahydrobiopterin Deficiency

Anatomical Context for Tetrahydrobiopterin Deficiency

Sources:
33MalaCards
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MalaCards organs/tissues related to Tetrahydrobiopterin Deficiency:

33
Brain, T cells, Endothelial, Fetal brain

Animal Models for Tetrahydrobiopterin Deficiency or affiliated genes

Sources:
37MGI, 28inGenious Targeting Laboratory
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Publications for Tetrahydrobiopterin Deficiency

Sources:
51PubMed
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Articles related to Tetrahydrobiopterin Deficiency:

(show top 50)    (show all 91)
idTitleAuthorsYear
1
Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan. (22832064)
2013
2
Testing for tetrahydrobiopterin responsiveness in patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. (23436109)
2013
3
Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow. (21512164)
2011
4
Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience. (21416196)
2011
5
Molecular characterization of phenylketonuria and tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Japan. (21307867)
2011
6
Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency. (21402147)
2011
7
Maternal tetrahydrobiopterin deficiency: the course of two pregnancies and follow-up of two children in a mother with 6-pyruvoyl-tetrahydropterin synthase deficiency. (19322676)
2009
8
Tetrahydrobiopterin deficiency in human rabies. (18949578)
2009
9
Genotype-predicted tetrahydrobiopterin (BH4)-responsiveness and molecular genetics in Croatian patients with phenylalanine hydroxylase (PAH) deficiency. (19394257)
2009
10
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. (17935162)
2008
11
Study on tetrahydrobiopterin deficiency in Northern Chinese population]. (16767663)
2006
12
Can the DCoHalpha isozyme compensate in patients with 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH deficiency? (16423549)
2006
13
Tetrahydrobiopterin deficiency exaggerates intimal hyperplasia after vascular injury. (15774769)
2005
14
Screening and diagnosis of tetrahydrobiopterin responsive phenylalanine hydroxylase deficiency with tetrahydrobiopterin loading test]. (15924746)
2005
15
Reversible parkinsonism following heroin pyrolysate inhalation is associated with tetrahydrobiopterin deficiency. (15390004)
2004
16
In vivo studies of phenylalanine hydroxylase by phenylalanine breath test: diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. (15319459)
2004
17
Cranial MR spectroscopy of tetrahydrobiopterin deficiency. (12063241)
2002
18
Screening of tetrahydrobiopterin deficiency among hyperphenylalaninemic patients]. (11937441)
2002
19
Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency. (11592814)
2001
20
Identification of three novel 6-pyruvoyl-tetrahydropterin synthase gene mutations (226C>T, IVS3+1G>A, 116-119delTGTT) in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency. (11438997)
2001
21
Reconstitution of a metabolic pathway with triple-cistronic IRES-containing retroviral vectors for correction of tetrahydrobiopterin deficiency. (10765502)
2000
22
Screening for 6-pyruvoyl-tetrahydrobiopterin synthase (PTPS) deficiency: clinical analysis of 9 patients with PTPS deficiency]. (11798810)
2000
23
Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. (10861247)
2000
24
Hyperprolactinemia, a tool in treatment control of tetrahydrobiopterin deficiency: endocrine studies in an affected girl. (9545000)
1998
25
Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency. (8707300)
1996
26
Retrovirus-mediated gene transfer of 6-pyruvoyl-tetrahydropterin synthase corrects tetrahydrobiopterin deficiency in fibroblasts from hyperphenylalaninemic patients. (8864759)
1996
27
Monitoring treatment in tetrahydrobiopterin deficiency by serum prolactin. (8739973)
1996
28
Monoamine oxidase inhibitors in tetrahydrobiopterin deficiency. (8801112)
1995
29
Antenatal diagnosis of tetrahydrobiopterin deficiency by quantification of pterins in amniotic fluid and enzyme activity in fetal and extrafetal tissue. (7923811)
1994
30
Tetrahydrobiopterin deficiency in Portugal: results of the screening for hyperphenylalaninemia. (7508163)
1993
31
Experimental research on a fetal treatment for tetrahydrobiopterin deficiency. (8304124)
1993
32
Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment. (8433887)
1993
33
Tetrahydrobiopterin and quinonoid dihydrobiopterin concentrations in CSF from patients with dihydropteridine reductase deficiency. (7609464)
1993
34
Tetrahydrobiopterin deficiency and an international database of patients. (8304121)
1993
35
Response of 6-pyruvoyl-tetrahydropterin synthase deficiency to tetrahydrobiopterin. (1588012)
1992
36
Attempt at treatment with tetrahydrobiopterin in combined deficiency of xanthine oxidase and sulphite oxidase. (1779639)
1991
37
Gastrointestinal serotonin: depletion due to tetrahydrobiopterin deficiency induced by 2,4-diamino-6-hydroxypyrimidine administration. (1825228)
1991
38
Early neurotoxicity of high-dose of methotrexate and tetrahydrobiopterin deficiency]. (1793349)
1991
39
Strategy for the screening of tetrahydrobiopterin deficiency among hyperphenylalaninaemic patients: 15-years experience. (1886401)
1991
40
On-off phenomenon in a child with tetrahydrobiopterin deficiency due to 6-pyruvoyl tetrahydropterin synthase deficiency (BH4 deficiency). (2646129)
1989
41
Tetrahydrobiopterin and "non-responsive" dihydropteridine reductase deficiency. (2885683)
1987
42
"Peripheral" tetrahydrobiopterin deficiency with hyperphenylalaninaemia due to incomplete 6-pyruvoyl tetrahydropterin synthase deficiency or heterozygosity. (3297709)
1987
43
Tetrahydrobiopterin in dihydropteridine reductase deficiency. (3945285)
1986
44
A model for hyperphenylalaninaemia due to tetrahydrobiopterin deficiency. (3088325)
1986
45
Differential diagnosis of tetrahydrobiopterin deficiency. (3930839)
1985
46
Blood spots on Guthrie cards can be used for inherited tetrahydrobiopterin deficiency screening in hyperphenylalaninaemic infants. (6696496)
1984
47
Dihydropteridine reductase deficiency: non-response to oral tetrahydrobiopterin load test. (6434829)
1984
48
A case of tetrahydrobiopterin deficiency due to a defective synthesis of dihydrobiopterin. (6820430)
1982
49
Early diagnosis of hyperphenylalaninemia due to tetrahydrobiopterin deficiency (malignant hyperphenylalaninemia). (7365585)
1980
50
Atypical phenylketonuria due to tetrahydrobiopterin deficiency. Diagnosis and treatment with tetrahydrobiopterin, dihydrobiopterin and sepiapterin. (445845)
1979

Genetic Variations for Tetrahydrobiopterin Deficiency

Expression for genes affiliated with Tetrahydrobiopterin Deficiency

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Tetrahydrobiopterin Deficiency

Search GEO for disease gene expression data for Tetrahydrobiopterin Deficiency.

Pathways for genes affiliated with Tetrahydrobiopterin Deficiency

Sources:
38NCBI BioSystems Database, 12EMD Millipore, 54Reactome, 30KEGG, 4Cell Signaling Technology
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Compounds for genes affiliated with Tetrahydrobiopterin Deficiency

Sources:
45Novoseek, 11DrugBank, 24HMDB, 29IUPHAR, 50PharmGKB, 60Tocris Bioscience
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Compounds related to Tetrahydrobiopterin Deficiency according to GeneCards/GeneDecks:

(show top 50)    (show all 146)
idCompoundScoreTop Affiliating Genes
1estrogen4510.0TPH1, PCBD1, GCH1
27-biopterin4510.0QDPR, PCBD1, PAH
3Biopterin119.9SPR, PTS, DHFR
4dihydroneopterin triphosphate45 2410.9PTS, SPR, GCH1
5glutamate459.9PTS, TPH1, HPRT1
67,8-Dihydrobiopterin119.8TH, PCBD1, PAH
7tetrahydropterin459.8PAH, TH, TPH1
8neopterin459.5QDPR, PAH, PTS, TPH1, GCH1
9oxygen45 2410.4TPH1, PTS, NOS1, PAH
10(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin119.4NOS3, NOS1, PAH
114a-hydroxytetrahydrobiopterin45 2410.4GCH1, TPH1, PAH, TH, PCBD1
12dihydrofolate459.3SPR, PAH, DHFR, QDPR, GCH1
136-pyruvoyltetrahydropterin459.3TH, PTS, SPR, PCBD1, GCH1, QDPR
14carbidopa45 2910.1PRL, TH, PTS, TPH1
15catecholamine459.1TPH1, PTS, TH, QDPR, GCH1, PAH
16ptio459.1NOS1, SOD1, NOS3
17mdma459.0TPH1, PRL, TH
18onoo458.9NOS1, SOD1, NOS3
19gtp45 299.9SPR, PTS, PAH, TH, GCH1, QDPR
20s-nitroso-n-acetylpenicillamine458.9TPH1, NOS3, SOD1, NOS1
21allopurinol45 50 1110.8NOS3, SOD1, HPRT1, NOS1
22valine458.8PAH, TPH1, NOS1, DHFR, HPRT1
23dopamine45 29 11 2411.8PTS, GCH1, QDPR, TPH1, SPR, NOS1
24phenylalanine458.6GCH1, QDPR, PCBD1, TH, PAH, PTS
25l-nmma458.6SOD1, GH1, NOS1, NOS3
26dihydropteridine45 249.5PCBD1, DHFR, TH, GCH1, QDPR, PAH
27dmso458.5TPH1, NOS1, HPRT1, GH1, SOD1
285-hydroxytryptophan458.4TPH1, PTS, TH, QDPR, GH1, PRL
29melatonin45 60 29 11 2412.4TPH1, SPR, GCH1, PAH, PRL, GH1
30opiate458.3TH, PRL, HPRT1, GH1
31norepinephrine45 11 2410.3QDPR, PRL, GCH1, SPR, TH, PAH
32peroxynitrite458.3TPH1, NOS3, SOD1, NOS1
33methotrexate45 50 1110.2DHFR, HPRT1, NOS1, QDPR, GH1, NOS3
34acetylcholine45 50 29 11 2412.2GH1, TPH1, QDPR, NOS1, TH, NOS3
35folate458.2GCH1, QDPR, HPRT1, DHFR, NOS3, NOS1
36glutamine458.2NOS1, PAH, TH, DHFR, HPRT1, GH1
37h2o2458.2TH, PAH, PTS, TPH1, GCH1, QDPR
38sodium nitroprusside458.1SOD1, GH1, TH, NOS3, NOS1, TPH1
39pterin45 249.1QDPR, PCBD1, DHFR, TH, NOS1, PAH
40pteridine458.1SPR, PTS, GCH1, QDPR, DHFR, TH
41nadph45 248.9QDPR, SPR, PTS, NOS3, DHFR, NOS1
42nitric oxide45 11 249.8SPR, NOS1, PTS, PAH, TPH1, GCH1
43ascorbic acid45 248.7TPH1, PTS, NOS1, NOS3, DHFR, SOD1
44alanine457.6PAH, QDPR, SOD1, GH1, NOS1, DHFR
45sepiapterin45 248.6PCBD1, TH, NOS3, NOS1, PAH, PTS
46dihydrobiopterin45 248.4TPH1, SPR, GCH1, QDPR, PCBD1, DHFR
47tetrahydrobiopterin45 11 249.4TH, NOS3, NOS1, PAH, SPR, DHFR
48cysteine457.4TH, DHFR, HPRT1, GH1, SOD1, TPH1
49levodopa45 118.3GCH1, SOD1, GH1, PRL, TPH1, PTS
50arginine456.1TPH1, PTS, PAH, NOS1, NOS3, DHFR

GO Terms for genes affiliated with Tetrahydrobiopterin Deficiency

Sources:
16Gene Ontology
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Cellular components related to Tetrahydrobiopterin Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1neuron projectionGO:0430059.6TPH1, TH, QDPR
2cytoplasmic vesicleGO:0314109.0GCH1, SOD1, TH
3cytoplasmGO:0057376.8PCBD1, QDPR, SOD1, GCH1, HPRT1, TH
4cytosolGO:0058296.3TPH1, GCH1, SOD1, QDPR, PCBD1, HPRT1

Biological processes related to Tetrahydrobiopterin Deficiency according to GeneCards/GeneDecks:

(show all 25)
idNameGO IDScoreTop Affiliating Genes
1catecholamine biosynthetic processGO:04242310.0TH, PAH
2L-phenylalanine catabolic processGO:00655910.0PAH, PCBD1, QDPR
3dopamine biosynthetic processGO:0424169.9TH, GCH1
4positive regulation of guanylate cyclase activityGO:0312849.7NOS1, NOS3
5negative regulation of hydrolase activityGO:0513469.7NOS3, NOS1
6neurotransmitter biosynthetic processGO:0421369.6PAH, NOS1, TH
7arginine catabolic processGO:0065279.6NOS1, NOS3
8tetrahydrobiopterin biosynthetic processGO:0067299.6SPR, PTS, PCBD1, QDPR, GCH1
9response to amphetamineGO:0019759.5TH, HPRT1, SOD1
10response to nutrient levelsGO:0316679.5TH, SOD1
11negative regulation of potassium ion transportGO:0432679.5NOS3, NOS1
12nitric oxide metabolic processGO:0462099.4GCH1, NOS3, PTS, SPR
13regulation of nitric-oxide synthase activityGO:0509999.4GCH1, NOS3, PTS, SPR
14negative regulation of blood pressureGO:0457769.4GCH1, NOS3, NOS1
15multicellular organismal response to stressGO:0335559.4PRL, NOS1
16nitric oxide mediated signal transductionGO:0072639.4NOS1, NOS3
17regulation of blood pressureGO:0082179.3NOS3, SOD1, GCH1
18cellular nitrogen compound metabolic processGO:0346419.3QDPR, PCBD1, TH, PAH, TPH1
19nitric oxide biosynthetic processGO:0068099.2GCH1, NOS3, NOS1, SPR
20response to heatGO:0094089.2SOD1, NOS3, NOS1
21positive regulation of JAK-STAT cascadeGO:0464279.1PRL, GH1
22response to estradiol stimulusGO:0323559.0TH, PRL, GH1
23response to ethanolGO:0454718.9SOD1, PRL, TH
24response to lipopolysaccharideGO:0324968.7GCH1, PRL, TH
25small molecule metabolic processGO:0442817.6GCH1, QDPR, PCBD1, HPRT1, TH, NOS3

Molecular functions related to Tetrahydrobiopterin Deficiency according to GeneCards/GeneDecks:

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1amino acid bindingGO:0165979.7TPH1, PAH, TH
2nitric-oxide synthase activityGO:0045179.5NOS1, NOS3
3arginine bindingGO:0346189.5NOS3, NOS1
4NADPH-hemoprotein reductase activityGO:0039589.4NOS1, NOS3
5FMN bindingGO:0101819.4NOS1, NOS3
6NADP bindingGO:0506619.3NOS3, NOS1, SPR
7tetrahydrobiopterin bindingGO:0346179.3NOS1, NOS3, TH
8prolactin receptor bindingGO:0051489.2GH1, PRL
9cadmium ion bindingGO:0468709.1NOS1, NOS3
10iron ion bindingGO:0055069.0TPH1, PAH, NOS1, NOS3
11protein homodimerization activityGO:0428038.8GCH1, SOD1, QDPR, HPRT1, PTS

Products for genes affiliated with Tetrahydrobiopterin Deficiency

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Sources for Tetrahydrobiopterin Deficiency

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet