MCID: TTR005
MIFTS: 33

Tetrahydrobiopterin Deficiency

Categories: Blood diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Tetrahydrobiopterin Deficiency

MalaCards integrated aliases for Tetrahydrobiopterin Deficiency:

Name: Tetrahydrobiopterin Deficiency 77 54 26
Hyperphenylalaninemia Due to Tetrahydrobiopterin Deficiency 54 60 30 6
Hyperphenylalaninemia, Non-Phenylketonuric 54 26 74
Non-Phenylketonuric Hyperphenylalaninemia 54 26 60
Hyperphenylalaninemia Caused by a Defect in Biopterin Metabolism 54 26
Hyperphenylalaninemia Due to Bh4 Deficiency 54 60
Bh4 Deficiency 54 26

Characteristics:

Orphanet epidemiological data:

60
hyperphenylalaninemia due to tetrahydrobiopterin deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

Classifications:



External Ids:

ICD10 via Orphanet 35 E70.1
UMLS via Orphanet 75 C0751435 C0751436
Orphanet 60 ORPHA238583
UMLS 74 C0751436

Summaries for Tetrahydrobiopterin Deficiency

NIH Rare Diseases : 54 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 acidphenylalanine, 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.

MalaCards based summary : Tetrahydrobiopterin Deficiency, also known as hyperphenylalaninemia due to tetrahydrobiopterin deficiency, is related to hyperphenylalaninemia, bh4-deficient, a and hyperphenylalaninemia, bh4-deficient, b. An important gene associated with Tetrahydrobiopterin Deficiency is GCH1 (GTP Cyclohydrolase 1). The drugs Verapamil and Nitric Oxide have been mentioned in the context of this disorder. Affiliated tissues include brain and endothelial.

Genetics Home Reference : 26 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 : 77 Tetrahydrobiopterin deficiency (THBD, BH4D), also called THB or BH4 deficiency, is a rare metabolic... more...

Related Diseases for Tetrahydrobiopterin Deficiency

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



Diseases related to Tetrahydrobiopterin Deficiency

Symptoms & Phenotypes for Tetrahydrobiopterin Deficiency

Drugs & Therapeutics for Tetrahydrobiopterin Deficiency

Drugs for Tetrahydrobiopterin Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 16)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Verapamil Approved Phase 2 52-53-9 2520
2
Nitric Oxide Approved Phase 2 10102-43-9 145068
3
Calcium Approved, Nutraceutical Phase 2 7440-70-2 271
4
Vitamin C Approved, Nutraceutical Phase 2 50-81-7 5785 54670067
5 Vasodilator Agents Phase 2
6 phenylalanine Phase 2
7 Anti-Arrhythmia Agents Phase 2
8 Hormones Phase 2
9 calcium channel blockers Phase 2
10 Calcium, Dietary Phase 2
11 Protective Agents Phase 2
12 Micronutrients Phase 2
13 Vitamins Phase 2
14 Trace Elements Phase 2
15 Nutrients Phase 2
16 Antioxidants Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency Completed NCT00355264 Phase 2 Phenoptin
2 A Phase 2, Pharmacokinetic Study of the Effects of 6R-BH4 Alone or 6R-BH4 With Vitamin C in Subjects With Endothelial Dysfunction Completed NCT00532844 Phase 2 6R-BH4 (sapropterin dihydrochloride);6R-BH4 (sapropterin dihydrochloride)
3 A Study of the Effects of 6R-BH4 on Blood Pressure in Subjects With Poorly Controlled Systemic Hypertension Completed NCT00325962 Phase 2 6R-BH4 (sapropterin dihydrochloride)
4 A Study of CNSA-001 in Primary Tetrahydrobiopterin Deficient Patients With Hyperphenylalaninemia Recruiting NCT03519711 Phase 1, Phase 2 CNSA-001
5 Retrospective Observational Safety Effectiveness With Kuvan in hpA Completed NCT03864029 KUVAN
6 Observational Study on the Long Term Safety of Kuvan® Treatment in Patients With Hyperphenylalaninemia (HPA) Due to Phenylketonuria (PKU) or BH4 Deficiency Active, not recruiting NCT01016392

Search NIH Clinical Center for Tetrahydrobiopterin Deficiency

Genetic Tests for Tetrahydrobiopterin Deficiency

Genetic tests related to Tetrahydrobiopterin Deficiency:

# Genetic test Affiliating Genes
1 Hyperphenylalaninemia Due to Tetrahydrobiopterin Deficiency 30

Anatomical Context for Tetrahydrobiopterin Deficiency

MalaCards organs/tissues related to Tetrahydrobiopterin Deficiency:

42
Brain, Endothelial

Publications for Tetrahydrobiopterin Deficiency

Articles related to Tetrahydrobiopterin Deficiency:

(show top 50) (show all 67)
# Title Authors Year
1
Gene mutation and pedigree analysis of tetrahydrobiopterin deficiency in a Uygur family of China. ( 30221392 )
2018
2
Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients. ( 30001213 )
2018
3
Tetrahydrobiopterin deficiency in the pathogenesis of Fabry disease. ( 28158561 )
2017
4
Massive parallel sequencing as a new diagnostic approach for phenylketonuria and tetrahydrobiopterin-deficiency in Thailand. ( 28915855 )
2017
5
Long-term safety and effectiveness of pramipexole in tetrahydrobiopterin deficiency. ( 27562098 )
2016
6
Endothelial cell tetrahydrobiopterin deficiency attenuates LPS-induced vascular dysfunction and hypotension. ( 26276526 )
2015
7
Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia. ( 25418970 )
2015
8
Target Prolactin Range in Treatment of Tetrahydrobiopterin Deficiency. ( 26515614 )
2015
9
Diagnosis, treatment and follow-up of patients with tetrahydrobiopterin deficiency in Shandong province, China. ( 25304915 )
2014
10
Tetrahydrobiopterin deficiency induces gastroparesis in newborn mice. ( 23639814 )
2013
11
The proportion of tetrahydrobiopterin deficiency and PAH gene deficiency variants among cases with hyperphenyalaninemia in Western Iran. ( 24497712 )
2013
12
Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: results of a retrospective, multicentre study. ( 23138986 )
2013
13
Long-term follow-up of tetrahydrobiopterin therapy in patients with tetrahydrobiopterin deficiency in Japan. ( 22832064 )
2013
14
Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow. ( 21512164 )
2011
15
Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience. ( 21416196 )
2011
16
Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency. ( 21402147 )
2011
17
Autophagy induction by tetrahydrobiopterin deficiency. ( 21795851 )
2011
18
Lessons from 30 years of selective screening for tetrahydrobiopterin deficiency. ( 20458544 )
2010
19
Sapropterin dihydrochloride for phenylketonuria and tetrahydrobiopterin deficiency. ( 30780801 )
2010
20
[The investigation of differential diagnostic development and incidence of tetrahydrobiopterin deficiency]. ( 19534905 )
2009
21
Tetrahydrobiopterin deficiency in human rabies. ( 18949578 )
2009
22
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
23
[Mutation analysis and one novel mutation detection of 6-pyruvoyl tetrahydropterin synthase gene in children with tetrahydrobiopterin deficiency]. ( 18505119 )
2008
24
Outcome and long-term follow-up of 36 patients with tetrahydrobiopterin deficiency. ( 18060820 )
2008
25
Proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus. ( 17679617 )
2007
26
Tetrahydrobiopterin availability, nitric oxide metabolism and glutathione status in the hph-1 mouse; implications for the pathogenesis and treatment of tetrahydrobiopterin deficiency states. ( 17242981 )
2007
27
[Study on tetrahydrobiopterin deficiency in Northern Chinese population]. ( 16767663 )
2006
28
Tetrahydrobiopterin deficiency exaggerates intimal hyperplasia after vascular injury. ( 15774769 )
2005
29
Tetrahydrobiopterin deficiency and dopamine loss in a genetic mouse model of Lesch-Nyhan disease. ( 15159647 )
2004
30
Reversible parkinsonism following heroin pyrolysate inhalation is associated with tetrahydrobiopterin deficiency. ( 15390004 )
2004
31
GTP cyclohydrolase I gene transfer reverses tetrahydrobiopterin deficiency and increases nitric oxide synthesis in endothelial cells and isolated vessels from diabetic rats. ( 15467010 )
2004
32
[Screening of tetrahydrobiopterin deficiency among hyperphenylalaninemic patients]. ( 11937441 )
2002
33
Reduced nitric oxide metabolites in CSF of patients with tetrahydrobiopterin deficiency. ( 11902126 )
2002
34
Cranial MR spectroscopy of tetrahydrobiopterin deficiency. ( 12063241 )
2002
35
Screening for tetrahydrobiopterin deficiency among hyperphenylalaninemia patients in Southern China. ( 11940335 )
2002
36
Tetrahydrobiopterin deficiency increases neuronal vulnerability to hypoxia. ( 12358762 )
2002
37
Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS. ( 10874306 )
2000
38
Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. ( 10861247 )
2000
39
Reconstitution of a metabolic pathway with triple-cistronic IRES-containing retroviral vectors for correction of tetrahydrobiopterin deficiency. ( 10765502 )
2000
40
Hyperprolactinemia, a tool in treatment control of tetrahydrobiopterin deficiency: endocrine studies in an affected girl. ( 9545000 )
1998
41
Retrovirus-mediated gene transfer of 6-pyruvoyl-tetrahydropterin synthase corrects tetrahydrobiopterin deficiency in fibroblasts from hyperphenylalaninemic patients. ( 8864759 )
1996
42
Monitoring treatment in tetrahydrobiopterin deficiency by serum prolactin. ( 8739973 )
1996
43
Monoamine oxidase inhibitors in tetrahydrobiopterin deficiency. ( 8801112 )
1995
44
Tetrahydrobiopterin deficiency and brain nitric oxide synthase in the hph1 mouse. ( 7542713 )
1995
45
Antenatal diagnosis of tetrahydrobiopterin deficiency by quantification of pterins in amniotic fluid and enzyme activity in fetal and extrafetal tissue. ( 7923811 )
1994
46
Possible high frequency of tetrahydrobiopterin deficiency in south Brazil. ( 7967477 )
1994
47
Tetrahydrobiopterin deficiency and an international database of patients. ( 8304121 )
1993
48
Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. ( 8326489 )
1993
49
Tetrahydrobiopterin deficiency in Portugal: results of the screening for hyperphenylalaninemia. ( 7508163 )
1993
50
Experimental research on a fetal treatment for tetrahydrobiopterin deficiency. ( 8304124 )
1993

Variations for Tetrahydrobiopterin Deficiency

ClinVar genetic disease variations for Tetrahydrobiopterin Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 GCH1 NM_000161.2(GCH1): c.206C> T (p.Pro69Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs56127440 GRCh37 Chromosome 14, 55369176: 55369176
2 GCH1 NM_000161.2(GCH1): c.206C> T (p.Pro69Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs56127440 GRCh38 Chromosome 14, 54902458: 54902458

Expression for Tetrahydrobiopterin Deficiency

Search GEO for disease gene expression data for Tetrahydrobiopterin Deficiency.

Pathways for Tetrahydrobiopterin Deficiency

GO Terms for Tetrahydrobiopterin Deficiency

Sources for Tetrahydrobiopterin Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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