We report a case of a 46-year-old Japanese woman with hereditary progressive dystonia with marked diurnal fluctuations and dopa-responsive dystonia (HPD/DRD). She developed difficulty in walking at the age of 44 years due to bradykinesia as well as hand tremors, muscle rigidity, increased tendon reflexes and mild dystonia in the lower extremities, all of which responded remarkably to low doses of levodopa (150 mg/day). Biopterin and neopterin concentrations in the cerebrospinal fluid (CSF) were decreased. Analysis of the guanosine 5'-triphosphate cyclohydrolase I (GCH1) gene revealed a novel mutation (W53X) in one allele. The GCH1 activity that was expressed in mononuclear blood cells was almost half the normal value (usually 2-20% of the normal value (39.0+/-9.2 pmol/ml) in patients with HPD/DRD). The relatively conserved GCH1 activity that is expressed in stimulated peripheral blood mononuclear cells may be related to the late clinical symptoms in this patient.
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Functional movement disorders in dopa-responsive dystonia.
Parkinsonism Relat Disord
January 2025
Institute of Systems Motor Science, University Medical Center Schleswig-Holstein, University of Lübeck, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Center of Rare Diseases, University Medical Center Schleswig-Holstein, Lübeck, Germany. Electronic address:
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Pathogenic Variant in the 5'-Untranslated Region of and Clinical Heterogeneity in a Chinese Family with Dopa-Responsive Dystonia.
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Department of General Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Background: Variants in the gene, encoding guanosine triphosphate cyclohydrolase, are associated with dopa-responsive dystonia (DRD) and are considered risk factors for parkinson's disease.
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Article Synopsis
- - Dopa-responsive dystonia (DRD) is a genetic disorder characterized by symptoms similar to Parkinson's disease and dystonia, caused by changes in the GCH1 gene affecting dopamine production.
- - This case report is unique as it connects childhood-onset DRD with amyotrophic lateral sclerosis (ALS), indicating a potential link between these two conditions.
- - The findings suggest that the diverse genetic backgrounds in the North African population might play a role in the occurrence of multiple related disorders.
Striatal cell-type-specific molecular signatures reveal therapeutic targets in a model of dystonia.
bioRxiv
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Department of Pharmacology and Chemical Biology, Emory University, Atlanta, GA, USA.
Article Synopsis
- Striatal dysfunction is linked to various types of dystonia, such as idiopathic and inherited forms, with the striatum housing different types of GABAergic neurons that control movement.
- Research using a model of DOPA-responsive dystonia (DRD) revealed that dSPNs and iSPNs exhibit distinct molecular changes that contribute to the disorder, highlighting a specific dysregulation in glutamatergic signaling for both neuron types.
- The differences in how these neurons adapt due to dopamine deficiencies suggest potential biochemical targets for therapies, emphasizing that the impact of dopamine loss on movement disorders varies depending on the timing and the specific neuron type affected.
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