Dopa-responsive Dystonia

A hereditary DYSTONIA where symptoms similar to those of PARKINSON DISEASE arise in early childhood; it responds favorably to treatment with LEVODOPA. Germline mutations in the GCH1 gene have been identified. OMIM: 128230

Also Known As:

Dystonia, Dopa-responsive; Dopa-Responsive Dystonia; Dopa-responsive dystonia, autosomal dominant; Dystonia 5; Dystonia, Dopa-responsive, autosomal dominant; Dystonia, progressive, with diurnal variation; Dystonia-Parkinsonism with diurnal fluctuation; Hereditary Progressive Dystonia with Marked Diurnal Fluctuation; Segawa syndrome, autosomal dominant

Networked: 290 relevant articles (13 outcomes, 17 trials/studies)

Relationship Network

Disease Context: Research Results

Nervous System Diseases: 14178
- Central Nervous System Diseases: 4213
  - Movement Disorders: 4634
    - Dystonic Disorders: 807
      - Dopa-responsive Dystonia: 290

Related Diseases

1.	Dystonia (Limb Dystonia)
2.	Dyskinesias (Dyskinesia)
3.	Movement Disorders (Movement Disorder)
4.	Parkinsonian Disorders (Parkinsonism)
5.	Phenylketonurias (Phenylketonuria)

Experts

1.	Klein, Christine: 7 articles (01/2022 - 01/2014)
2.	Furukawa, Yoshiaki: 7 articles (01/2020 - 05/2002)
3.	Ichinose, Hiroshi: 7 articles (01/2019 - 05/2004)
4.	Opladen, Thomas: 6 articles (01/2022 - 12/2010)
5.	Blau, Nenad: 5 articles (03/2013 - 09/2004)
6.	Segawa, Masaya: 5 articles (03/2011 - 01/2003)
7.	Haavik, Jan: 4 articles (11/2021 - 01/2007)
8.	Bhatia, Kailash P: 4 articles (12/2015 - 06/2009)
9.	Blau, N: 4 articles (11/2004 - 03/2001)
10.	Furukawa, Y: 4 articles (07/2003 - 04/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Dopa-responsive Dystonia:

1.	Levodopa (L Dopa)FDA LinkGeneric 06/01/2012 - "[Diagnosis of dopa-responsive dystonia after 34 years: complete remission after L-dopa treatment]." 07/01/2009 - "Patient with mutation in the PARK2 gene had Dopa-responsive dystonia with a good improvement with L-Dopa, similar to Dopa-responsive dystonia secondary to GCH1 mutations. " 06/01/1998 - "With levodopa substitution the patients with dopa responsive dystonia improved clinically as well as in quantitative tests on hand tapping, verbal and performance IQ, concept formation, and set shifting abilities." 10/01/2017 - "A trial of levodopa can be both diagnostic and therapeutic in children with dopa-responsive dystonia. " 01/01/2022 - "Case Report: Clinical Outcome From Pallidal Stimulation in a Patient With Levodopa-Resistant Dopa-Responsive Dystonia."
2.	Dopamine (Intropin)FDA LinkGeneric 01/01/2011 - "Dopamine is extremely effective in dopa-responsive dystonia. " 06/01/2021 - "Dopa-responsive dystonia (DRD) and DRD plus are diseases of the dopamine pathway with sizeable genetic diversity and myriad presentations. " 09/01/2016 - "Dopa-responsive dystonia (DRD) and DRD-plus are inherited metabolic disorders of the dopamine synthetic pathway that have considerable clinical, biochemical, and genetic heterogeneity. " 06/01/2010 - "Dopa responsive dystonia results from abnormalities in the dopamine synthesis pathway which produces an array of phenotypic presentations with equally numerous genotypes. " 07/01/2009 - "Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia."
3.	Proteins (Proteins, Gene)FDA Link 01/01/2021 - "Fifty-seven of the 1805 proteins identified were differentially regulated in DOPA-responsive dystonia mice compared to control mice. " 01/01/2021 - "Differential expression of striatal proteins in a mouse model of DOPA-responsive dystonia reveals shared mechanisms among dystonic disorders." 01/01/2019 - "This manuscript provides an overview of the role of human TH in the pathophysiology of PD, covering the following aspects: (1) structures of the gene and protein of human TH in relation to PD; (2) similarity and dissimilarity between the phenotypes of aging-related sPD and those of young-onset fPD or DOPA-responsive dystonia due to DA deficiency in the striatum with decreased TH activity caused by mutations in either the TH gene or GTP cyclohydrolase I (GCH1) gene; and (3) genetic variants of the TH gene (polymorphisms, rare variants, and mutations) in PD, as discovered recently by advanced genome analysis." 01/01/2003 - "Genetics and biochemistry of dopa-responsive dystonia: significance of striatal tyrosine hydroxylase protein loss." 05/01/2002 - "Our data suggest that the extent of striatal tyrosine hydroxylase protein loss may be critical in determining dopa-responsive dystonia symptomatology."
4.	Dihydroxyphenylalanine (Dopa)IBA 07/01/1991 - "The 6 patients with typical dopa-responsive dystonia had a modest but significant reduction in the uptake of tracer into both caudate and putamen, which indicates a defect in the decarboxylation, vesicular uptake, and storage of [18F]dopa. " 04/01/2007 - "Some patients received the dopa treatment for diagnosis of dopa-responsive dystonia (DRD). " 03/01/1994 - "We report cerebrospinal fluid monoamine metabolite analyses and 6-[18F]fluoro-1-dopa positron emission tomography (FD-PET) from an asymptomatic carrier of the gene for dopa-responsive dystonia. " 07/01/1991 - "We have studied [18F]dopa uptake in 6 patients with classic dopa-responsive dystonia (5 familial patients and 1 sporadic patient), aged 18 to 66 years. " 07/01/1991 - "Dopa-responsive dystonia: [18F]dopa positron emission tomography."
5.	Carbidopa (Lodosyn)FDA LinkGeneric 01/01/2016 - "As is typical in dopa-responsive dystonia, these patients displayed dramatic improvement with L-dopa/carbidopa therapy. "
6.	Tyrosine 3-Monooxygenase (Tyrosine Hydroxylase)IBA 07/01/2014 - "Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia." 04/02/2023 - "Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. " 04/02/2023 - "[Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations]." 01/01/2022 - "Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase (TH) gene is rare, we found that the clinical manifestations of seven children with tyrosine hydroxylase gene mutations are similar to dopa-responsive dystonia. " 01/01/2020 - "We present a case of mild, adult-onset dopa-responsive dystonia (DRD) with a heterozygous mutation in the tyrosine hydroxylase (TH) gene. "
7.	EnzymesIBA 09/01/2008 - "Hereditary diseases such as DOPA-responsive dystonia and atypical phenylketonuria are known to be caused by coding or splice-site mutations in the GCH1 gene, leading mostly to a dominant negative enzyme. " 01/01/2020 - "Mild dopa-responsive dystonia in heterozygous tyrosine hydroxylase mutation carrier: Evidence of symptomatic enzyme deficiency? " 01/01/2020 - "Comment on "Mild dopa-responsive dystonia in heterozygous tyrosine hydroxylase mutation carrier: Evidence of symptomatic enzyme deficiency?"" 01/01/2020 - "Mild dopa-responsive dystonia in heterozygous tyrosine hydroxylase mutation carrier: Evidence of symptomatic enzyme deficiency?" 01/01/2010 - "Recently, a type of dopa-responsive dystonia (DRD) (DYT5, Segawa's disease) was revealed to be caused by dominant mutations of the gene encoding GTP cyclohydrolase I (GCHI), which is the rate-limiting enzyme of BH(4) biosynthesis. "
8.	GTP Cyclohydrolase (GTP Cyclohydrolase I)IBA 02/06/2018 - "Dopa-Responsive Dystonia in Han Chinese Patients: One Novel Heterozygous Mutation in GTP Cyclohydrolase 1 (GCH1) and Three Known Mutations in TH." 01/01/2018 - "A novel missense mutation of the GTP cyclohydrolase 1 gene in a Taiwanese family with dopa-responsive dystonia: A case report." 12/01/2017 - "GTP cyclohydrolase 1-deficient DOPA-responsive dystonia, caused by autosomal dominant mutation in the gene coding for GTP cyclohydrolase 1, is a rare disorder with a reported prevalence of 0.5 per million. " 12/01/2017 - "In patients with GTP-cyclohydrolase deficient dopa-responsive dystonia (DRD) the occurrence of associated non-motor symptoms (NMS) is to be expected. " 01/01/2017 - "Dopa-responsive dystonia (DRD) has largely been associated with autosomal dominant mutations in the GCH1 gene leading to GTP cyclohydrolase 1 deficiency. "
9.	sapropterin (tetrahydrobiopterin)FDA Link 01/01/2021 - "GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson's disease (PD) and tetrahydrobiopterin (BH4 )-deficient hyperphenylalaninemia B. " 09/01/2001 - "Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency." 03/01/2001 - "Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts." 01/01/2022 - "Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). " 03/01/1988 - "Effect of tetrahydrobiopterin and 5-hydroxytryptophan on hereditary progressive dystonia with marked diurnal fluctuation: a suggestion of the serotonergic system involvement."
10.	BiopterinsIBA 05/01/2002 - "In the autopsied putamen of an asymptomatic GCH1 mutation carrier, we found that brain biopterin loss (-82%) paralleled that reported in dopa-responsive dystonia patients (-84%). " 08/01/1998 - "Influence of development and aging on brain biopterin: implications for dopa-responsive dystonia onset." 03/01/2001 - "Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts." 09/01/2004 - "The search for mutations in genes coding for components of the biopterin pathway other than GTPCH1 revealed a mutation in the gene coding for sepiapterin reductase (SPR) in 1 of 95 patients with GCH1-negative dopa-responsive dystonia (DRD). " 05/01/2002 - "It is assumed that brain biopterin and dopamine loss should not be as severe in asymptomatic dopa-responsive dystonia caused by GCH1 mutations as it is in symptomatic dopa-responsive dystonia. "

Therapies and Procedures

1.	Therapeutics 07/16/2005 - "Segawa's disease, or dopa-responsive dystonia, responds extremely well to therapy, whereas the other entities respond in varying ways to the different therapeutic alternatives. " 04/01/2002 - "Dopa - Responsive Dystonia are characterized by marked diurnal fluctuations of the dystonic symptoms and by their marked and sustained response to dopaminergic therapy; associated parkinsonian signs are usually observed later in the course of the disease. " 06/01/1994 - "Because of the dramatic response to therapy, dopa-responsive dystonia must be considered in the differential diagnosis of disorders presenting as gait disorders in childhood." 05/01/2000 - "For a small minority of patients (eg, those with dopa-responsive dystonia, Wilson's disease, or psychogenic dystonia), specific therapy directed at one of the many causes of dystonia is available. " 01/01/2012 - "Since the efficacy of DBS is the improvement in dopaminergic drug-sensitive motor symptoms, we offer surgery to patients only when medical therapy has failed; (1) severe motor fluctuations, (2) severe dyskinesia, (3) tremor uncontrollable by medications, (4) painful dystonia, (5) side-effect for medication (drug-induced psychosis, nausea, vomitting). "
2.	Deep Brain Stimulation 06/01/2011 - "The authors present a case of medically intractable dopa-responsive dystonia in a 6-year-old boy whose condition significantly improved with bilateral subthalamic nucleus deep brain stimulation. " 04/01/2020 - "The aim of this study was to observe the improvement in patients with dopa-responsive dystonia (DRD) after deep brain stimulation (DBS) of the globus pallidus internus (GPi). " 04/01/2020 - "Deep Brain Stimulation for the Treatment of Dopa-Responsive Dystonia: A Case Report and Literature Review." 06/01/2011 - "Bilateral subthalamic nucleus deep brain stimulation for dopa-responsive dystonia in a 6-year-old child."
3.	Aftercare (After-Treatment) 02/01/1995 - "We report on a 5 year old girl who has hereditary progressive dystonia with marked diurnal fluctuation that improved remarkably after treatment with L-dopa. "
4.	Transcranial Direct Current Stimulation 01/01/2015 - "Eight people with dystonia (5 writer's dystonia, 3 musician's dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. "
5.	Precision Medicine 11/12/2021 - "Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia-A Focus on Tyrosine Hydroxylase Deficiency."