A Distonia Responsiva à Dopa (DRD) descreve um grupo de doenças que afetam os nervos e o metabolismo do corpo. Elas são caracterizadas por distonia, que costuma apresentar variações ao longo do dia, e que responde muito bem à levodopa (L-dopa). A DRD inclui a distonia responsiva à dopa de padrão genético dominante (DYT5a), a distonia responsiva à dopa de padrão genético recessivo (DYT5b), e a distonia responsiva à dopa causada pela deficiência da enzima sepiapterina redutase (SR).
Introdução
O que você precisa saber de cara
A Distonia Responsiva à Dopa (DRD) descreve um grupo de doenças que afetam os nervos e o metabolismo do corpo. Elas são caracterizadas por distonia, que costuma apresentar variações ao longo do dia, e que responde muito bem à levodopa (L-dopa). A DRD inclui a distonia responsiva à dopa de padrão genético dominante (DYT5a), a distonia responsiva à dopa de padrão genético recessivo (DYT5b), e a distonia responsiva à dopa causada pela deficiência da enzima sepiapterina redutase (SR).
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 48 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 98 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
6 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive, Not applicable.
Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development (PubMed:15716272, PubMed:17184956). It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity)
CytoplasmNucleus
Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
An autosomal dominant disorder characterized by global developmental delay affecting motor, cognitive, and speech domains apparent in early childhood or infancy. Most patients also show movement abnormalities, often hypotonia with later development of dopa-responsive dystonia or parkinsonism. About half of patients develop various types of seizures.
Required for synaptic transmission regulation (PubMed:33539324). It probably controls the recruitment of voltage-gated calcium channels to the presynaptic membrane, and modulates neurotransmitter release
CytoplasmMitochondrion
Dystonia 22, adult-onset
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT22AO is an autosomal recessive form characterized by focal dystonia or tremor and mild cognitive impairment.
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (PubMed:7763314, PubMed:7903306). Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism (PubMed:14766016). It may also have a role in the development of malignancy and the growth progress
CytoplasmNucleusCytoplasm, cytosol
Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (PubMed:15287903, PubMed:1680128, PubMed:17391063, PubMed:24753243, PubMed:34922205, PubMed:8528210, Ref.18). In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity).
Cytoplasm, perinuclear regionNucleusCell projection, axonCytoplasmCytoplasmic vesicle, secretory vesicle, synaptic vesicle
Segawa syndrome autosomal recessive
A form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA.
Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown
CytoplasmNucleus
Hyperphenylalaninemia, BH4-deficient, B
A disease characterized by malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency, and defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia. In this intermediate phenotype, there is marked motor delay, but no intellectual disability and only minimal, if any, hyperphenylalaninemia.
Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin
Cytoplasm
Dystonia, DOPA-responsive, due to sepiapterin reductase deficiency
A form of DOPA-responsive dystonia. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.
Variantes genéticas (ClinVar)
195 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 1,272 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
15 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Distonia sensível à dopa
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Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
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Outros ensaios clínicos
4 ensaios clínicos encontrados, 1 ativos.
Publicações mais relevantes
Clinical and genetic spectrum of L-dopa responsive dystonia: insights from seven Egyptian cases.
Dopa-responsive dystonia (DRD) encompasses a group of treatable movement disorders with significant clinical and genetic heterogeneity. Despite being treatable, DRD is often misdiagnosed, leading to delays in therapy. This retrospective study aims to describe the clinical and genetic features of seven Egyptian patients from four unrelated families with confirmed DRD. Medical records were reviewed to document clinical data, neuroimaging, and genetic testing. We identified six patients with Tyrosine hydroxylase-deficient DRD and one with GTP cyclohydrolase 1 deficiency. The age at onset of initial symptoms ranged from 0.6 to 1.5 years. Universal clinical features included motor delay, weakness, and delayed speech and language development. Neuroimaging findings showed periventricular demyelination in two patients and brain atrophic changes in one. We identified two previously reported variants in the TH gene (c.-70G > A and c.938G > T) and one novel variant in the GCH1 gene (c.343 + 1G > A). All patients, except one, showed a complete response to L-dopa therapy within the first six months of treatment. This first Egyptian cohort highlights DRD as a treatable yet underdiagnosed cause of dystonia in the Middle East. We report a novel GCH1 variant and TH-related type A phenotypes, underscoring the importance of early genetic diagnosis and levodopa therapy.
Novel Pathogenic GCH1 Variant in Familial DOPA-Responsive Dystonia.
Two adolescent female patients, who were referred independently of each other, presented with progressive gait disturbances that worsened over the course of the day. Symptoms began in early childhood with foot instability and progressed to clubfoot, pain, and limping. MRI of the neuroaxis did not reveal any central nervous system abnormalities. Genetic testing identified the same intronic variant of uncertain significance in GCH1 in both individuals. Subsequent investigations uncovered a previously unrecognized familial relationship between the two patients, belonging to an extended family in which six women were affected by a gait disorder. Previous diagnoses within the family included childhood-onset spasticity and psoriatic arthritis. The familial GCH1 variant was confirmed in all symptomatic individuals, as well as in two asymptomatic female carriers. RNA sequencing revealed a splicing defect caused by the GCH1 near splice-site variant. A robust clinical response to L-DOPA therapy confirmed the diagnosis of DOPA-responsive dystonia (DRD) in this family. This case highlights the phenotypic variability of DRD, which frequently leads to misdiagnosis and delays in appropriate treatment. Careful assessment of family history and recognition of diurnal symptom fluctuations are key to identifying this highly treatable condition.
Long-term efficiency of pallidal DBS and the role of Levodopa treatment in DYT-GNAL and 18p deletion syndrome associated dystonia: an observational study and review of literature.
Dystonia due to loss-of-function variants in the GNAL gene in DYT-GNAL and 18p-deletion (18pdel) syndrome has been reported to respond well to pallidal deep brain stimulation (GPi-DBS) occasionally, but long-term data is scarce. GNAL is implicated in dopamine receptor function, which may explain anecdotal reports of hypokinesia in DYT-GNAL and 18pdel-associated dystonia, a phenomenon that has not yet been systematically reviewed. We retrospectively evaluated a cohort of three patients with GNAL variants treated with GPi-DBS, documenting individual long-term outcomes spanning up to 25 years. Dystonia severity was assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke - Fahn - Marsden Dystonia Rating Scale (BFMDRS). We also documented bradykinetic symptoms and levodopa response. A literature review was added focusing on DBS outcomes and the effects of levodopa in DYT-GNAL and 18pdel-associated dystonia. In our patients, TWSTRS severity subscale I was reduced by 63% in early (≤ 12months; 20.7 to 7.7 points) and 81% in late follow-up (> 12months; 20.7 to 4 points) after GPi-DBS χ. BFMDRS decreased by 67% and 44%; each with a Kendall's coefficient of 0.78, indicating a high degree of concordance in improvement trajectories. Two patients exhibited bradykinesia, which was levodopa-responsive in one. GPi-DBS responses have been reported for another ten DYT-GNAL and two 18pdel-patients. Bradykinesia prompted levodopa challenges in 15 patients, resulting in improvement in five. Long-term follow-up data from three DYT-GNAL patients treated with DBS showed sustained improvement in dystonia, particularly in cervical symptoms. Bradykinesia may be an inherent clinical feature of GNAL-related dystonia, warranting further investigation.
A rare GCH1 p.Arg170Gly variant shows impaired enzymatic activity and co-occurs with a novel NEXMIF p.Asp155GlnfsTer2 leading to a complex neurological phenotype: functional studies and clinical aspects.
GTP cyclohydrolase I deficiency is a rare inherited disorder of biogenic amine metabolism due to pathogenic GCH1 variants, manifesting as DOPA-responsive dystonia or severe encephalopathy. Pathogenic variants in the NEXMIF gene cause X-linked intellectual disability and epilepsy. Here, using trio-WES approach, we identified a rare, previously uncharacterized GCH1 p.Arg170Gly variant and a novel NEXMIF p.Asp155GlnfsTer2 variant in a female patient. This study aimed to confirm the pathogenicity of these variants and elucidate their underlying molecular pathomechanisms by molecular in vitro studies. First, we confirmed that the NEXMIF variant introduces a premature stop codon at the cDNA level, implying loss of NEXMIF protein function. To explore the functional consequences of the GCH1 variant, we expressed and purified wild-type (WT) and p.Arg170Gly homodecameric GCH1, as well as a mixed population of heterodecameric GCH1 proteins, and performed biochemical characterization. Kinetic studies revealed that the catalytic efficiency of the mutant homo- and heterodecameric GCH1 was reduced by 37- and 9-fold, respectively, compared to the WT enzyme, confirming a significant loss of activity. Furthermore, the presence of mutant GCH1 monomers negatively affected catalytic cooperativity in the decameric enzyme. Circular dichroism indicated that p.Arg170Gly slightly impacts the structure of the protein, as shown by reduced α-helical content in the mutant homodecamer. In summary, we provide the first functional evidence that the GCH1 p.Arg170Gly variant is pathogenic mainly due to reduced enzyme activity, and that its combination with a novel NEXMIF loss-of-function variant manifests as a complex neurological phenotype arising from two distinct disorders.
Phenotypic and genotypic heterogeneity in a series of cases associated with dopa-responsive dystonia.
Dopa-responsive dystonia (DRD) includes a group of neurological disorders that manifest with lower limb dystonia and an excellent response to levodopa. Parkinsonism is commonly associated with DRD, and many cases of GCH1 gene mutations without dystonia but with evidence of nigrostriatal pathway degeneration, indistinguishable to idiopathic Parkinson's disease (PD), have been recently described. This phenotypic variability has been observed even among members of the same family. Clinical and genetic description of 14 patients from 4 different families with DRD associated mutations. The results showed GCH1 mutations in three of the four families, while one family had a mutation in the SPR gene. Within patients with GCH1 mutations, two showed DRD symptoms, five had PD phenotype, and four were asymptomatic. The only patient with SPR mutation clinically displayed symptoms of dystonia and parkinsonism. DaTscan® revealed degeneration of the nigroestriatal pathway in two PD patients. Furthermore, phenotypic variability of the same mutation was observed in two families. DRD associated mutations have a heterogeneous clinical expression GCH1 gene mutations can be manifested with PD phenotype along with the degeneration of the nigroestiatal pathway. Therefore, GCH1 gene testing might be useful in cases of PD suggestive of genetic origin or with family history of dystonia.
Publicações recentes
Long-Term Outcomes in Tyrosine Hydroxylase Deficiency: A Case Series of Four Paediatric Patients.
Genetic analysis reveals phenotypic variability in three Colombian families with dopa-responsive dystonia: novel genotype-phenotype correlations.
Clinical and genetic spectrum of L-dopa responsive dystonia: insights from seven Egyptian cases.
Long-term efficiency of pallidal DBS and the role of Levodopa treatment in DYT-GNAL and 18p deletion syndrome associated dystonia: an observational study and review of literature.
A rare GCH1 p.Arg170Gly variant shows impaired enzymatic activity and co-occurs with a novel NEXMIF p.Asp155GlnfsTer2 leading to a complex neurological phenotype: functional studies and clinical aspects.
📚 EuropePMC342 artigos no totalmostrando 196
Clinical and genetic spectrum of L-dopa responsive dystonia: insights from seven Egyptian cases.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyLong-term efficiency of pallidal DBS and the role of Levodopa treatment in DYT-GNAL and 18p deletion syndrome associated dystonia: an observational study and review of literature.
Journal of neural transmission (Vienna, Austria : 1996)A rare GCH1 p.Arg170Gly variant shows impaired enzymatic activity and co-occurs with a novel NEXMIF p.Asp155GlnfsTer2 leading to a complex neurological phenotype: functional studies and clinical aspects.
Molecular genetics and metabolismPhenotypic and genotypic heterogeneity in a series of cases associated with dopa-responsive dystonia.
NeurologiaL-DOPA in diurnal fluctuating dystonia: two different clinical presentations, one treatment.
NeurogeneticsNovel Pathogenic GCH1 Variant in Familial DOPA-Responsive Dystonia.
NeuropediatricsConsensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase (TH) Deficiency.
Journal of inherited metabolic diseasePhenotypic, Genotypic Characteristics, and Treatment Strategies of Pediatric Tyrosine Hydroxylase Deficiency: A Single-Center Retrospective Analysis of 51 Cases.
Movement disorders clinical practiceCombined molecular characterization and dopa-responsive treatment in two patients with NR4A2-associated intellectual developmental disorder.
Frontiers in geneticsGenetic and clinical profile of a Brazilian cohort of dopa-responsive dystonia.
Journal of the neurological sciencesDopa-responsive dystonia and young-onset parkinsonism in a patient with heterozygous mutation in SPR and PRKN treated with pallidal stimulation.
NeurologiaAdult-onset Huntington's disease with unusual presentation of dopa-responsive lower limb dystonia.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyStriatal cell-type-specific molecular signatures reveal potential therapeutic targets in a model of dystonia.
Neurobiology of diseaseDopa-responsive dystonia and phenotypes associated with TH gene variants: a systematic review and Mexican case series.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyRetinal Thickness in Patients with Parkinson's Disease and Dopa Responsive Dystonia-Is There Any Difference?
BiomedicinesNovel Phenotypes and Deep Intronic Variant Expand TH-Associated Dopa-Responsive Dystonia Spectrum.
Annals of clinical and translational neurologyDopa responsive dystonia due to a GCH1 gene variant mimicking hereditary spastic paraparesis.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyRetrospective chart review of inherited and idiopathic dystonia.
Frontiers in geneticsClinical and Basic Research on Dopa-Responsive Dystonia: Neuropathological and Neurochemical Findings.
Juntendo medical journalClinical Reasoning: Juvenile-Onset Dopa-Responsive Dystonia-Until It Isn't.
NeurologyNovel Aspects of Hereditary Spastic Paraplegia: A Clinicopathologic and Biochemical Study of a Patient With a Heterozygous GCH1 Variant.
Neuropathology and applied neurobiologyFunctional movement disorders in dopa-responsive dystonia.
Parkinsonism & related disordersPathogenic Variant in the 5'-Untranslated Region of GCH1 and Clinical Heterogeneity in a Chinese Family with Dopa-Responsive Dystonia.
Tremor and other hyperkinetic movements (New York, N.Y.)An Open-Label Pilot Study to Examine the Safety, Tolerability and Efficacy of Deutetrabenazine in Isolated Dystonia.
Movement disorders clinical practiceAssociation of Amyotrophic Lateral Sclerosis and Dopa-responsive dystonia in a Tunisian patient.
Parkinsonism & related disordersStriatal cell-type-specific molecular signatures reveal therapeutic targets in a model of dystonia.
bioRxiv : the preprint server for biologyNeuroregression in Two Siblings Due to Dopa-Responsive Dystonia (DRD)- Plus.
Indian journal of pediatricsCompound Heterozygous WARS2 Variants Including a Hypomorphic Allele Cause a Milder Phenotype of Complex Dopa Responsive Dystonia: Case Report and Review of the Literature.
Cerebellum (London, England)Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes.
Movement disorders clinical practiceDe novo p.Glu61Ter mutation in GCH1 in a Moroccan patient with dopa-responsive dystonia: a case report.
The Pan African medical journalChloroprocaine 3% for anesthesia during cesarean section in a patient with dopa-responsive dystonia: A case report.
MedicineCompound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes.
International journal of developmental neuroscience : the official journal of the International Society for Developmental NeuroscienceThree-Dimensional Gait Analysis as a Biomarker for GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia.
Pediatric neurologyMaternal Uniparental Isodisomy of Chromosome 2 Leading to Homozygous Variants in SPR and ZNF142 : A Case Report and Review of the UPD2 Literature.
Global medical geneticsAn Inversion Affecting the GCH1 Gene as a Novel Finding in Dopa-Responsive Dystonia.
Movement disorders clinical practiceDopa-responsive dystonia and paroxysmal dystonic attacks associated with ATP1A3 gene variant.
Practical neurologyGenetic testing for non-parkinsonian movement disorders: Navigating the diagnostic maze.
Parkinsonism & related disordersMechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model.
European journal of pharmacologyLevodopa for Dystonia in Children: A Case Series and Review of the Literature.
Pediatric neurologyTyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1.
Journal of inherited metabolic diseaseGTP cyclohydroxylase1 (GCH1): Role in neurodegenerative diseases.
GeneCatecholamines and Parkinson's disease: tyrosine hydroxylase (TH) over tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH1) to cytokines, neuromelanin, and gene therapy: a historical overview.
Journal of neural transmission (Vienna, Austria : 1996)A Novel Variant of GCH1 in Dopa-Responsive Dystonia With Oculogyric Crises and Intrafamilial Phenotypic Heterogeneity.
Journal of movement disordersCrucial neuroprotective roles of the metabolite BH4 in dopaminergic neurons.
bioRxiv : the preprint server for biologyDopa-responsive dystonia in Bulgarian patients: report of three cases.
European journal of human genetics : EJHGDopa-responsive dystonia in spinocerebellar ataxia 6: A case report.
Clinical neurology and neurosurgeryDystonic Cerebral Palsy Phenotype Due to GNAO1 Variant Responsive to Levodopa.
Tremor and other hyperkinetic movements (New York, N.Y.)[Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations].
Zhonghua er ke za zhi = Chinese journal of pediatricsDopa-Responsive Dystonia: An Early Presentation of Ataxia-Telangiectasia.
Annals of Indian Academy of NeurologyStriatal Subregion-selective Dysregulated Dopamine Receptor-mediated Intracellular Signaling in a Model of DOPA-responsive Dystonia.
NeuroscienceHeterozygous pathogenic variation in GCH1 associated with treatable severe spastic tetraplegia.
Parkinsonism & related disordersGut Microbiome Composition in Dystonia Patients.
International journal of molecular sciencesSegawa syndrome caused by TH gene mutation and its mechanism.
Frontiers in geneticsMethylation of the serotonin reuptake transporter gene and non-motor symptoms in dystonia patients.
Clinical epigeneticsProlonged Episodic Dystonia in Tyrosine Hydroxylase Deficiency Due to Homozygous c.698G>A (p.Arg233His) Mutation-A Diagnostic Challenge.
Movement disorders clinical practiceCase Report: Severe Hypotonia Without Hyperphenylalaninemia Caused by a Homozygous GCH1 Variant: A Case Report and Literature Review.
Frontiers in geneticsGenetic intersection between dystonia and neurodevelopmental disorders: Insights from genomic sequencing.
Parkinsonism & related disordersTime estimation and arousal responses in dopa-responsive dystonia.
Scientific reportsA Case of Dopa Responsive Dystonia Presenting as Isolated Foot Dystonia.
Journal of neurosciences in rural practiceRecurrent Biallelic p.L347P PINK1 Variant in Polynesians with Parkinsonism and Isolated Dopa-Responsive Dystonia.
Movement disorders clinical practice[Analysis of GCH1 gene variant in a consanguineous Chinese pedigree affected with tetrahydrobiopterin deficiency].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsNeuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia.
Molecular genetics and metabolism reportsCase Report: Clinical Outcome From Pallidal Stimulation in a Patient With Levodopa-Resistant Dopa-Responsive Dystonia.
Frontiers in neurologySPG11 presenting with dystonic tremor in childhood.
Parkinsonism & related disordersSerotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients.
Scientific reportsClinical, neuroradiological, and molecular characterization of patients with atypical Zellweger spectrum disorder caused by PEX16 mutations: a case series.
NeurogeneticsRecessive GCH1 Deficiency Causing DOPA-Responsive Dystonia Diagnosed by Reported Negative Exome.
PediatricsPARK2 Patient Presenting with Dopa-Responsive Dystonia.
Case reports in neurologyLongitudinal evaluations of somatosensory-motor inhibition in Dopa-responsive dystonia.
Parkinsonism & related disordersRecognizing Atypical Dopa-Responsive Dystonia and Its Mimics.
Neurology. Clinical practiceTreatable Hyperkinetic Movement Disorders Not to Be Missed.
Frontiers in neurologyRelationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review.
Movement disorders : official journal of the Movement Disorder SocietyGenetic landscape of Segawa disease in Spain. Long-term treatment outcomes.
Parkinsonism & related disordersGCH1 Deficiency Activates Brain Innate Immune Response and Impairs Tyrosine Hydroxylase Homeostasis.
The Journal of neuroscience : the official journal of the Society for NeurosciencePersonalized Medicine to Improve Treatment of Dopa-Responsive Dystonia-A Focus on Tyrosine Hydroxylase Deficiency.
Journal of personalized medicineA Practical Approach to Early-Onset Parkinsonism.
Journal of Parkinson's diseaseDopaminergic and serotonergic alterations in plasma in three groups of dystonia patients.
Parkinsonism & related disordersCase Report: Guitarist's cramp as the initial manifestation of dopa-responsive dystonia with a novel heterozygous GCH1 mutation.
F1000ResearchThe Genetic Landscape of Parkinsonism-Related Dystonias and Atypical Parkinsonism-Related Syndromes.
International journal of molecular sciencesA Case of GCH-1 Mutation Dopa-Responsive Dystonia Requiring High Doses of Levodopa for Treatment.
Tremor and other hyperkinetic movements (New York, N.Y.)Multimodal Longitudinal Neurophysiological Investigations in Dopa-Responsive Dystonia.
Movement disorders : official journal of the Movement Disorder SocietyDifferential expression of striatal proteins in a mouse model of DOPA-responsive dystonia reveals shared mechanisms among dystonic disorders.
Molecular genetics and metabolismIdentification of TH Variants in Chinese Dopa-Responsive Dystonia Patients and Long-Term Outcomes.
Frontiers in neurologyOlder-onset levodopa-responsive parkinsonism with normal DAT-SPECT and pterin hypometabolism.
BMJ case reportsSeries of Dopa Responsive Dystonia Masquerading as Other Diseases with Short Review.
Journal of pediatric neurosciencesNeurometabolic causes of dystonia: Sepiapterin reductase-deficient dopamine- and serotonin-responsive dystonia-plus syndrome.
Journal of the neurological sciencesMolecular and metabolic bases of tetrahydrobiopterin (BH4) deficiencies.
Molecular genetics and metabolismInter and intra-generational phenotypic variability in a Portuguese family with DYT-GCH1.
Parkinsonism & related disordersEarly-onset autosomal dominant GTP-cyclohydrolase I deficiency: Diagnostic delay and residual motor signs.
Brain & developmentGCH1 mutations in hereditary spastic paraplegia.
Clinical geneticsDopa-responsive dystonia, DRD-plus and DRD look-alike: a pragmatic review.
Acta neurologica BelgicaThe first case of Cri du Chat syndrome with dystonia.
Clinical neurology and neurosurgeryLevalbuterol lowers the feedback inhibition by dopamine and delays misfolding and aggregation in tyrosine hydroxylase.
Biochimie[Anesthesia in patients with dopa-responsive dystonia (Segawa syndrome) : Presentation of the pathophysiology, clinical picture and approach based on two case reports].
Der AnaesthesistClinical Application of Whole Exome Sequencing to Identify Rare but Remediable Neurologic Disorders.
Journal of clinical medicineIncreased superoxide in GCH1 mutant fibroblasts points to a dopamine-independent toxicity mechanism.
Parkinsonism & related disordersDifferences in Drug Pharmacokinetics and Motor Fluctuation in DYT-GCH1.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiquesNovel Protein Biomarkers of Monoamine Metabolism Defects Correlate with Disease Severity.
Movement disorders : official journal of the Movement Disorder SocietyCombined dystonias: clinical and genetic updates.
Journal of neural transmission (Vienna, Austria : 1996)Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeuticsBrain structural alterations in patients with GCH1 mutations associated DOPA-responsive dystonia.
Journal of neurology, neurosurgery, and psychiatryDopa-responsive dystonia caused by tyrosine hydroxylase deficiency: Three cases report and literature review.
MedicineDegradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease and Dopa-Responsive Dystonia.
International journal of molecular sciencesElectroconvulsive Therapy and Dopa-Responsive Dystonia: Improvements in Neurological Symptoms After Electroconvulsive Therapy Treatment.
The journal of ECTWhole exome sequencing identified a new compound heterozygous PRKN mutation in a Chinese family with early-onset Parkinson's disease.
Bioscience reportsManagement of Parkinson's Disease During Pregnancy: Literature Review and Multidisciplinary Input.
Movement disorders clinical practiceJuvenile Parkinsonism with PARK2 Gene Mutation Misdiagnosed as Dopa-responsive Dystonia: a Case Report.
Brain & NeuroRehabilitationMild dopa-responsive dystonia in heterozygous tyrosine hydroxylase mutation carrier: Evidence of symptomatic enzyme deficiency? Response from the authors.
Parkinsonism & related disordersAutosomal dominant GCH1 mutations causing spastic paraplegia at disease onset.
Parkinsonism & related disordersClinical and Genetic Heterogeneity in a Cohort of Chinese Children With Dopa-Responsive Dystonia.
Frontiers in pediatricsDopa-Responsive Dystonia: A Male Patient Inherited a Novel GCH1 Deletion from an Asymptomatic Mother.
Journal of movement disordersAmyotrophic onset in GCH1 dopa-responsive dystonia.
Iranian journal of neurologyMild dopa-responsive dystonia in heterozygous tyrosine hydroxylase mutation carrier: Evidence of symptomatic enzyme deficiency?
Parkinsonism & related disordersChild Neurology: A young child with an undiagnosed case of dystonia responsive to l-dopa.
NeurologyA case of late-onset dopa-responsive isolated dystonia secondary to a novel tyrosine hydroxylase gene variant.
Clinical parkinsonism & related disordersDeep Brain Stimulation for the Treatment of Dopa-Responsive Dystonia: A Case Report and Literature Review.
World neurosurgeryLoss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.
Movement disorders : official journal of the Movement Disorder Society'Atypical' Parkinson's disease - genetic.
International review of neurobiologyGenetic study in a family with dopa-responsive dystonia revealed a novel mutation in sepiapterin reductase gene.
Pakistan journal of medical sciencesMyoclonus-dystonia: Distinctive motor and non-motor phenotype from other dystonia syndromes.
Parkinsonism & related disordersA Severe l-Dopa Responsive Dystonia With Slow and Continuous Improvement in a Patient With a Novel Mutation in the Tyrosine Hydroxylase Gene.
Movement disorders clinical practicePure hypotonia in a four-year-old patient: An atypical presentation of Dopa-responsive dystonia.
Journal of the neurological sciencesResidual signs of dopa-responsive dystonia with GCH1 mutation following levodopa treatment are uncommon in Korean patients.
Parkinsonism & related disordersGTP-Cyclohydrolase I deficiency presenting as malignant hyperphenylalaninemia, recurrent hyperthermia and progressive neurological dysfunction in a South Asian child - a case report.
BMC pediatricsA Compound Heterozygote for GCH1 Mutation Represents a Case of Atypical Dopa-Responsive Dystonia.
Journal of molecular neuroscience : MNPrenatal Genetic Testing for Dopa-Responsive Dystonia - Clinical Judgment in the Context of Next Generation Sequencing.
Journal of medicine and lifeA novel GTPCH deficiency mouse model exhibiting tetrahydrobiopterin-related metabolic disturbance and infancy-onset motor impairments.
Metabolism: clinical and experimentalDystonic crises in dopa-responsive dystonia induced by energy drinks.
Practical neurologyDopa-responsive dystonia.
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekkeThe quaternary structure of human tyrosine hydroxylase: effects of dystonia-associated missense variants on oligomeric state and enzyme activity.
Journal of neurochemistryCompound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia: A case report.
MedicineCommon and rare GCH1 variants are associated with Parkinson's disease.
Neurobiology of agingWhat a neurologist should know about PET and SPECT functional imaging for parkinsonism: A practical perspective.
Parkinsonism & related disordersMonoamine neurotransmitters and movement disorders in children and adults.
Revue neurologiqueHeterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease.
Frontiers in neurologyManagement of Psychosis in a Patient with Probable Dopa-Responsive Dystonia.
Case reports in psychiatryStriatal Cholinergic Interneurons in a Knock-in Mouse Model of L-DOPA-Responsive Dystonia.
Frontiers in systems neuroscienceHuman tyrosine hydroxylase in Parkinson's disease and in related disorders.
Journal of neural transmission (Vienna, Austria : 1996)Expanding the Spectrum of Dopa-Responsive Dystonia (DRD) and Proposal for New Definition: DRD, DRD-plus, and DRD Look-alike.
Journal of Korean medical scienceGCH1 mutations in dopa-responsive dystonia and Parkinson's disease.
Journal of neurologyGCH1 variants, tetrahydrobiopterin and their effects on pain sensitivity.
Scandinavian journal of painNeuropsychological Difficulties Associated with Dopa Responsive Dystonia.
Journal of pediatric neurosciencesStudy of GCH1 and TH genes in Chinese patients with Parkinson's disease.
Neurobiology of agingMutation in the GCH1 gene with dopa-responsive dystonia and phenotypic variability.
Neurology. GeneticsAtypical presentation of dopa-responsive dystonia in Taiwan.
Brain and behaviorHeterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity.
PainMotor fluctuations and levodopa-induced dyskinesias in dopa-responsive dystonia.
Parkinsonism & related disordersDopa-Responsive Dystonia in Han Chinese Patients: One Novel Heterozygous Mutation in GTP Cyclohydrolase 1 (GCH1) and Three Known Mutations in TH.
Medical science monitor : international medical journal of experimental and clinical researchVariability of presynaptic nigrostriatal dopaminergic function and clinical heterogeneity in a dopa-responsive dystonia family with GCH-1 gene mutation.
Journal of neurologyA novel missense mutation of the GTP cyclohydrolase 1 gene in a Taiwanese family with dopa-responsive dystonia: A case report.
Clinical neurology and neurosurgeryAn unusual presentation of tyrosine hydroxylase deficiency.
Journal of clinical movement disordersc.207C>G mutation in sepiapterin reductase causes autosomal dominant dopa-responsive dystonia.
Neurology. GeneticsA novel compound heterozygous TH mutation in a Japanese case of dopa-responsive dystonia with mild clinical course.
Parkinsonism & related disordersNon-motor symptoms and quality of life in dopa-responsive dystonia patients.
Parkinsonism & related disordersGCH1 mutations are common in Serbian patients with dystonia-parkinsonism: Challenging previously reported prevalence rates of DOPA-responsive dystonia.
Parkinsonism & related disordersParkinsonism without dopamine neuron degeneration in aged l-dopa-responsive dystonia knockin mice.
Movement disorders : official journal of the Movement Disorder SocietyDopa-responsive Dystonia in a Child Misdiagnosed as Cerebral Palsy.
Journal of pediatric neurosciencesTreatable inherited rare movement disorders.
Movement disorders : official journal of the Movement Disorder SocietyClinical Management of Dystonia in Childhood.
Paediatric drugsComplex and Dynamic Chromosomal Rearrangements in a Family With Seemingly Non-Mendelian Inheritance of Dopa-Responsive Dystonia.
JAMA neurology[Analysis of clinical phenotype and CGH1 gene mutations in a family affected with dopa-responsive dystonia].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsl-Dopa in dystonia: A modern perspective.
NeurologyTranslational effects and coding potential of an upstream open reading frame associated with DOPA Responsive Dystonia.
Biochimica et biophysica acta. Molecular basis of diseaseDopa-responsive dystonia presenting with predominant hemifacial dystonia.
Acta neurologica BelgicaAnesthetic considerations in scoliosis patient with dopa-responsive dystonia or Segawa's syndrome.
Journal of orthopaedic surgery (Hong Kong)Dopa-responsive dystonia in Chinese patients: Including a novel heterozygous mutation in the GCH1 gene with an intermediate phenotype and one case of prenatal diagnosis.
Neuroscience lettersDifferential diagnosis of Parkinson's disease and other neurodegenerative disorders.
Nihon rinsho. Japanese journal of clinical medicineL-DOPA therapy interferes with urine catecholamine analysis in children with suspected neuroblastoma: a case series.
Annals of clinical biochemistryNovel compound heterozygous synaptojanin-1 mutation causes l-dopa-responsive dystonia-parkinsonism syndrome.
Movement disorders : official journal of the Movement Disorder SocietyMild parkinsonian features in dystonia: Literature review, mechanisms and clinical perspectives.
Parkinsonism & related disordersDeep Brain Stimulation in Rare Inherited Dystonias.
Brain stimulationTranscranial sonography in dopa-responsive dystonia.
European journal of neurologyDopa-responsive dystonia or early-onset Parkinson disease - Genotype-phenotype correlation.
Neurologia i neurochirurgia polskaA novel tyrosine hydroxylase variant in a group of Chinese patients with dopa-responsive dystonia.
The International journal of neuroscienceA marked contrast between serotonergic and dopaminergic changes in dopa-responsive dystonia.
NeurologyClassification of dopa-responsive dystonia - a patient's perspective.
Nature reviews. NeurologyA Systematic Review of Treatment Outcome in Patients with Dopa-responsive Dystonia (DRD) and DRD-Plus.
Movement disorders clinical practiceDelayed Diagnosis of Dopa responsive Dystonia in Two Siblings.
Indian pediatricsLow frequency of GCH1 and TH mutations in Parkinson's disease.
Parkinsonism & related disordersA commentary on the utility of a new L-DOPA-responsive dystonia mouse model.
Rare diseases (Austin, Tex.)What Is Not in the Name? Dopa-Responsive Dystonia May Respond to More Than L-Dopa.
Pediatric neurology[Scans without Evidence of Dopamine Deficit (SWEDDs)].
Brain and nerve = Shinkei kenkyu no shinpoHan Chinese patients with dopa-responsive dystonia exhibit a low frequency of exonic deletion in the GCH1 gene.
Genetics and molecular research : GMRBrain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency.
Brain : a journal of neurologyPremotor-motor excitability is altered in dopa-responsive dystonia.
Movement disorders : official journal of the Movement Disorder SocietyDopamine or biopterin deficiency potentiates phosphorylation at (40)Ser and ubiquitination of tyrosine hydroxylase to be degraded by the ubiquitin proteasome system.
Biochemical and biophysical research communicationsA new knock-in mouse model of l-DOPA-responsive dystonia.
Brain : a journal of neurologyNucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts.
Molecular neurobiologyNonmotor Symptoms in Dopa-Responsive Dystonia.
Movement disorders clinical practiceSleep in patients with primary dystonia: A systematic review on the state of research and perspectives.
Sleep medicine reviewsDopa-responsive dystonia--clinical and genetic heterogeneity.
Nature reviews. NeurologyPre-movement gating of somatosensory evoked potentials in Segawa disease.
Brain & developmentGTP cyclohydrolase 1 mutations and Parkinson's disease: new insights beyond DOPA-responsive dystonia.
Movement disorders : official journal of the Movement Disorder SocietySPG11 Mutations Associated With a Complex Phenotype Resembling Dopa-Responsive Dystonia.
Movement disorders clinical practiceNovel GCH1 variant in Dopa-responsive dystonia and Parkinson's disease.
Parkinsonism & related disordersA requirement for Gch1 and tetrahydrobiopterin in embryonic development.
Developmental biologyAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Clinical and genetic spectrum of L-dopa responsive dystonia: insights from seven Egyptian cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology· 2026· PMID 41688735mais citado
- Novel Pathogenic GCH1 Variant in Familial DOPA-Responsive Dystonia.
- Long-term efficiency of pallidal DBS and the role of Levodopa treatment in DYT-GNAL and 18p deletion syndrome associated dystonia: an observational study and review of literature.
- A rare GCH1 p.Arg170Gly variant shows impaired enzymatic activity and co-occurs with a novel NEXMIF p.Asp155GlnfsTer2 leading to a complex neurological phenotype: functional studies and clinical aspects.
- Phenotypic and genotypic heterogeneity in a series of cases associated with dopa-responsive dystonia.
- Long-Term Outcomes in Tyrosine Hydroxylase Deficiency: A Case Series of Four Paediatric Patients.
- Genetic analysis reveals phenotypic variability in three Colombian families with dopa-responsive dystonia: novel genotype-phenotype correlations.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:255(Orphanet)
- MONDO:0016812(MONDO)
- Distonia e Espasticidade(PCDT · Ministério da Saúde)
- GARD:12144(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q689777(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
