B BH4-Deficient Hyperphenylalaninemia

mutation in GCH1

Also Known As:

Hyperphenylalaninemia, BH4-Deficient, B; GTP Cyclohydrolase I Deficiency; GTPCH deficiency; HPABH4B; Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To GTP Cyclohydrolase I Deficiency

Networked: 33 relevant articles (0 outcomes, 2 trials/studies)

Disease Context: Research Results

Nervous System Diseases: 14178
- Central Nervous System Diseases: 4213
  - Brain Diseases: 15694
    - Metabolic Brain Diseases: 215
      - Inborn Metabolic Brain Diseases: 2
        Phenylketonurias: 3454
        B BH4-Deficient Hyperphenylalaninemia: 33
Congenital, Hereditary, and Neonatal Diseases and Abnormalities: 933
- Inborn Genetic Diseases: 11939
  - Inborn Errors Metabolism: 1162
    - Inborn Metabolic Brain Diseases: 2
      - Phenylketonurias: 3454
        B BH4-Deficient Hyperphenylalaninemia: 33
    - Inborn Errors Amino Acid Metabolism: 1
      - Phenylketonurias: 3454
        B BH4-Deficient Hyperphenylalaninemia: 33
Nutritional and Metabolic Diseases: 15
- Metabolic Diseases: 10142
  - Inborn Errors Metabolism: 1162
    - Inborn Metabolic Brain Diseases: 2
      - Phenylketonurias: 3454
        B BH4-Deficient Hyperphenylalaninemia: 33
    - Inborn Errors Amino Acid Metabolism: 1
      - Phenylketonurias: 3454
        B BH4-Deficient Hyperphenylalaninemia: 33
  - Metabolic Brain Diseases: 215
    - Inborn Metabolic Brain Diseases: 2
      - Phenylketonurias: 3454
        B BH4-Deficient Hyperphenylalaninemia: 33

Related Diseases

1.	Phenylketonurias (Phenylketonuria)
2.	6-pyruvoyl-tetrahydropterin synthase deficiency
3.	Dopa-responsive Dystonia
4.	Dystonia (Limb Dystonia)
5.	Dyskinesias (Dyskinesia)

Experts

1.	Blau, Nenad: 7 articles (01/2021 - 12/2005)
2.	Thöny, Beat: 5 articles (05/2021 - 12/2005)
3.	Hoffmann, Georg F: 4 articles (09/2020 - 06/2011)
4.	Opladen, Thomas: 4 articles (03/2013 - 06/2011)
5.	Himmelreich, Nastassja: 2 articles (01/2021 - 09/2020)
6.	Shintaku, Haruo: 2 articles (03/2014 - 01/2009)
7.	Banno, Brian: 1 article (01/2022)
8.	Elbe, Dean: 1 article (01/2022)
9.	Friedlander, Robin: 1 article (01/2022)
10.	Horvath, Gabriella: 1 article (01/2022)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to B BH4-Deficient Hyperphenylalaninemia:

1.	Phenylalanine (L-Phenylalanine)FDA Link 01/01/2019 - "The different extents of BH4 reduction and phenylalanine accumulation observed between liver and brain in response to GTPCH deficiency gives potential new insights into the vulnerability of brain to GTPCH deficiency." 11/01/2012 - "Some patients with autosomal recessive GTPCH deficiency and all with sepiapterin reductase deficiency may be diagnosed late due to normal blood phenylalanine in NBS. " 06/01/2009 - "All these conditions can be identified in newborns by an elevated phenylalanine, with the exception of sepiapterin reductase and the dominant form of GTP cyclohydrolase I deficiency that results in biopterin deficiency/insufficiency only in the brain. " 06/01/2016 - "We report the case of a girl with autosomal recessive GTPCH deficiency, who was diagnosed at 14 months by means of an analysis of the cerebrospinal fluid with pterin, HVA and 5-HIAA deficiency, and positive phenylalanine overload test and genetic study. " 03/01/2013 - "Phenylalanine (Phe) loading test is a useful tool in the differential diagnosis of dopa-responsive dystonia due to autosomal dominant or recessive GTP cyclohydrolase I (GTPCH) deficiency or autosomal recessive sepiapterin reductase (SR) deficiency. "
2.	PterinsIBA 12/01/2005 - "We thus established reference values for pterins in blood spots in patients with hyperphenylalaninemia and identified new patients with GTP cyclohydrolase I deficiency, 6-pyruvoyl-tetrahydropterin synthase deficiency, and dihydropteridine reductase deficiency using dried blood spots on filter paper." 06/01/2016 - "We report the case of a girl with autosomal recessive GTPCH deficiency, who was diagnosed at 14 months by means of an analysis of the cerebrospinal fluid with pterin, HVA and 5-HIAA deficiency, and positive phenylalanine overload test and genetic study. "
3.	Hydroxyindoleacetic AcidIBA 06/01/2016 - "We report the case of a girl with autosomal recessive GTPCH deficiency, who was diagnosed at 14 months by means of an analysis of the cerebrospinal fluid with pterin, HVA and 5-HIAA deficiency, and positive phenylalanine overload test and genetic study. "
4.	GTP Cyclohydrolase (GTP Cyclohydrolase I)IBA 05/01/2008 - "We describe a unique presentation of autosomal recessive (AR) GTP cyclohydrolase I (GTPCH) deficiency, with severe CNS involvement but without hyperphenylalaninemia. " 05/15/1985 - "Increase of GTP cyclohydrolase I activity in mononuclear blood cells by stimulation: detection of heterozygotes of GTP cyclohydrolase I deficiency." 01/01/2016 - "A deficiency of GTP cyclohydrolase, encoded by the GCH1 gene, results in two neurological diseases: hyperphenylalaninaemia type HPABH4B and DOPA-responsive dystonia. " 12/01/1999 - "To explore the molecular etiology of two disorders caused by a defect in GTP cyclohydrolase I--hereditary progressive dystonia with marked diurnal fluctuation (HPD), also known as dopa-responsive dystonia (DRD), and autosomal recessive GTP cyclohydrolase I deficiency--we purified and analyzed recombinant human wild-type and mutant GTP cyclohydrolase I proteins expressed in Escherichia coli. " 03/01/2013 - "Phenylalanine (Phe) loading test is a useful tool in the differential diagnosis of dopa-responsive dystonia due to autosomal dominant or recessive GTP cyclohydrolase I (GTPCH) deficiency or autosomal recessive sepiapterin reductase (SR) deficiency. "
5.	EnzymesIBA 04/28/1995 - "We identified missense mutations in patients with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia coli to confirm alterations in the enzyme activity." 01/01/2011 - "Clinical characteristics and pahophysiologies of dopa-responsive dystonia are discussed by reviewing autosomal-dominant GTP cyclohydrolase-I deficiency (AD GCHI D), recessive deficiencies of enzymes of pteridine metabolism, and recessive tyrosine hydroxylase (TH). " 12/01/2000 - "In contrast, autosomal recessive GTP cyclohydrolase I deficiency with complete loss of the enzyme activity produces deficiencies of dopamine, norepinephrine, and serotonin and complex phenotypes with severe neurological symptoms (Ichinose et al, J Biol Chem 270, 10062-10071, 1995)." 06/01/2011 - "6-pyruvoyl-tetrahydropterin synthase and GTP cyclohydrolase I deficiency can be diagnosed by neopterin and biopterin analysis alone, while for diagnosis of dihydropteridine reductase deficiency additional determination of enzyme activity from the same DBS is essential. " 02/01/1984 - "GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia."
6.	6-pyruvoyltetrahydropterin synthase (PTPS)IBA 01/01/1996 - "Of these 308 patients, 181 suffered from 6-pyruvoyltetrahydropterin synthase deficiency, 92 from dihydropteridine reductase deficiency, 13 from pterin-4a-carbinolamine dehydratase deficiency, 12 from GTP cyclohydrolase I deficiency, and 10 are still unclassified. " 05/01/2021 - "Among the nine patients, we identified one with autosomal recessive GTP cyclohydrolase I (ar GTPCH) deficiency, two with 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, three with sepiapterin reductase (SR) deficiency, and three with DHPR deficiency. " 09/01/2020 - "In total 20 patients were diagnosed with PKU due to phenylalanine hydroxylase (PAH) deficiency, 2 with GTP cyclohydrolase I (GTPCH) deficiency, 6 with DHPR deficiency, and 3 with the 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. " 01/01/2017 - " results indicated that out of 76 cases involving BH4 deficiencies, 37 had 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, 35 had DHPR deficiency, 1 case had pterin-4a-carbinolamine dehydratase (PCD) deficiency, and 3 cases had GTP cyclohydrolase I (GTPCH) deficiency. " 06/01/2011 - "6-pyruvoyl-tetrahydropterin synthase and GTP cyclohydrolase I deficiency can be diagnosed by neopterin and biopterin analysis alone, while for diagnosis of dihydropteridine reductase deficiency additional determination of enzyme activity from the same DBS is essential. "
7.	NeopterinIBA 01/01/2019 - "GTP-Cyclohydrolase I deficiency (GTPCH) was identified based on normal dihydro pteridine reductase activity and markedly reduced neopterin in dried blood spot test. " 04/01/1999 - "Subsequently measured neopterin and biopterin synthesis in cytokine-stimulated skin fibroblasts confirmed GTPCH deficiency, albeit indirectly. " 04/01/1999 - "Urinary pteridine screening revealed very low levels of neopterin and biopterin which was highly suggestive of GTPCH deficiency. " 06/01/2011 - "6-pyruvoyl-tetrahydropterin synthase and GTP cyclohydrolase I deficiency can be diagnosed by neopterin and biopterin analysis alone, while for diagnosis of dihydropteridine reductase deficiency additional determination of enzyme activity from the same DBS is essential. " 04/01/1999 - "Low cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid concentrations, together with no detectable neopterin and decreased concentrations of biopterin and folate, agreed with the diagnosis of GTPCH deficiency. "
8.	Dopamine (Intropin)FDA LinkGeneric 12/01/2004 - "However, the pattern of changes observed is not that expected as a result of striatal dopamine deficiency and suggests that other effects of GTP cyclohydrolase I deficiency may be involved." 03/01/2014 - "GTPCH deficiency causes severe reduction of BH4, resulting in hyperphenylalaninemia (HPA) and decreased dopamine and serotonin synthesis. " 12/01/2000 - "In contrast, autosomal recessive GTP cyclohydrolase I deficiency with complete loss of the enzyme activity produces deficiencies of dopamine, norepinephrine, and serotonin and complex phenotypes with severe neurological symptoms (Ichinose et al, J Biol Chem 270, 10062-10071, 1995)." 02/01/1984 - "GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia."
9.	Neurotransmitter Agents (Neurotransmitter)IBA 01/01/2009 - "However, autosomal dominant GTPCH deficiency and autosomal recessive SR deficiency leads to BH4 and neurotransmitter deficiency without HPA and may not be detected by neonatal screening for phenylketonuria. " 01/01/2021 - "From a total of 324 alleles, 11 are associated with the autosomal recessive form of GTPCH deficiency presenting with hyperphenylalaninemia (HPA) and neurotransmitter deficiency, 295 GCH1 variant alleles are detected in the dominant form of L-dopa-responsive dystonia (DRD or Segawa disease) while phenotypes of 18 alleles remained undefined. " 01/01/2019 - "GTP cyclohydrolase I (GTPCH) deficiency could impair the synthesis of tetrahydrobiopterin and causes metabolic diseases involving phenylalanine catabolism, neurotransmitter synthesis, nitric oxide production and so on. "
10.	Serotonin (5 Hydroxytryptamine)IBA 03/01/2014 - "GTPCH deficiency causes severe reduction of BH4, resulting in hyperphenylalaninemia (HPA) and decreased dopamine and serotonin synthesis. " 12/01/2000 - "In contrast, autosomal recessive GTP cyclohydrolase I deficiency with complete loss of the enzyme activity produces deficiencies of dopamine, norepinephrine, and serotonin and complex phenotypes with severe neurological symptoms (Ichinose et al, J Biol Chem 270, 10062-10071, 1995)." 02/01/1984 - "GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia."

Therapies and Procedures

Therapeutics

01/01/2019 - "An appropriate GTPCH deficiency animal model with clinical symptoms, especially the motor impairments, is still not available for mechanism and therapy studies yet. "
08/01/2012 - "Prenatally initiated dopaminergic replacement therapy is beneficial and thus justified in AR GTPCH deficiency, allowing prevention of significant impairment of mental abilities."
08/01/2012 - "In the younger sibling, prenatal replacement therapy was initiated after a prenatal diagnosis of AR GTPCH deficiency was made. "
08/01/2012 - "To report the first prenatal dopaminergic replacement therapy in autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency without hyperphenylalaninemia. "
10/01/2004 - "Amantadine suppressed severe levodopa-induced choreic dyskinesia, which developed at initiation of levodopa therapy, in two siblings manifesting dystonia with motor delay phenotype of GTP cyclohydrolase I deficiency caused by compound heterozygous GCH1 mutations. "