Details of Disease

General Information of Disease (ID: DISMPJ7S)

• Disease Name: Dystonia 5
• Synonyms: dystonia, Dopa-responsive, autosomal dominant; DRD; dystonia, DOPA-responsive; Dopa-responsive dystonia, autosomal dominant; Segawa syndrome, autosomal dominant; dystonia, progressive, with diurnal variation; autosomal dominant dopa-responsive dystonia; Dopa-responsive dystonia; Segawa syndrome AD; dystonia-Parkinsonism with diurnal fluctuation; DYT5a; HPD with marked diurnal fluctuation; GTP cyclohydrolase 1-deficient dopa-responsive dystonia; dystonia, DOPA-responsive, with or without hyperphenylalaninemia; autosomal dominant Segawa syndrome; dystonia type 5; hereditary progressive dystonia with marked diurnal fluctuation; dystonia 5; DYT-GCH1; Segawa Syndrome; GTPCH1-deficient DRD; GTPCH1-deficient dopa-responsive dystonia
• Definition: Autosomal dominant dopa-responsive dystonia (DYT5a) is a rare neurometabolic disorder characterized by childhood-onset dystonia that shows a dramatic and sustained response to low doses of levodopa (L-dopa) and that may be associated with parkinsonism at an older age.
• Disease Hierarchy:
  DISEIJV9: Inherited dystonia
  DISCW5GN: Dopa-responsive dystonia
  DISFIL4X: GTP cyclohydrolase I deficiency
  DISMPJ7S: Dystonia 5
• Disease Identifiers:
  MONDO ID: MONDO_0007495
  MESH ID: C538007
  UMLS CUI: C1851920
  OMIM ID: 128230
  MedGen ID: 342121
  Orphanet ID: 98808
  SNOMED CT ID: 715768000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TH	TTUHP71	Limited	Altered Expression	[1]
HPD	TT8DSFC	moderate	Biomarker	[2]
SLC18A2	TTNZRI3	moderate	Altered Expression	[3]
SLC6A3	TTVBI8W	Strong	Biomarker	[4]
TOR1A	TTF85KW	Strong	Genetic Variation	[5]
GCH1	TTLSWP6	Definitive	Autosomal dominant	[6]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SPR	DEJVDAT	Strong	Genetic Variation	[7]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GNAL	OTESDTEU	Strong	Biomarker	[8]
MTG1	OTC9U1LI	Strong	Biomarker	[9]
SGCE	OT9F17JB	Strong	Genetic Variation	[10]
GCH1	OTOZ6NSL	Definitive	Autosomal dominant	[6]

References

• [1] The quaternary structure of human tyrosine hydroxylase: effects of dystonia-associated missense variants on oligomeric state and enzyme activity.J Neurochem. 2019 Jan;148(2):291-306. doi: 10.1111/jnc.14624. Epub 2018 Dec 9.
• [2] A novel missense mutation of the GTP cyclohydrolase I gene in a Korean family with hereditary progressive dystonia/dopa-responsive dystonia.Brain Dev. 2004 Aug;26(5):287-91. doi: 10.1016/S0387-7604(03)00167-0.
• [3] VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET.Synapse. 2003 Jul;49(1):20-8. doi: 10.1002/syn.10199.
• [4] GCH1 mutations in dopa-responsive dystonia and Parkinson's disease.J Neurol. 2018 Aug;265(8):1860-1870. doi: 10.1007/s00415-018-8930-8. Epub 2018 Jun 14.
• [5] Genetics of primary dystonia.Semin Neurol. 1999;19(3):271-80. doi: 10.1055/s-2008-1040843.
• [6] A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form. Neuroreport. 1999 Feb 25;10(3):487-91. doi: 10.1097/00001756-199902250-00008.
• [7] A novel tyrosine hydroxylase variant in a group of Chinese patients with dopa-responsive dystonia.Int J Neurosci. 2017 Aug;127(8):694-700. doi: 10.1080/00207454.2016.1236381. Epub 2016 Oct 5.
• [8] New genetic insights highlight 'old' ideas on motor dysfunction in dystonia.Trends Neurosci. 2013 Dec;36(12):717-25. doi: 10.1016/j.tins.2013.09.003. Epub 2013 Oct 18.
• [9] Non-motor symptoms and quality of life in dopa-responsive dystonia patients.Parkinsonism Relat Disord. 2017 Dec;45:57-62. doi: 10.1016/j.parkreldis.2017.10.005. Epub 2017 Oct 10.
• [10] Myoclonus-dystonia: Distinctive motor and non-motor phenotype from other dystonia syndromes.Parkinsonism Relat Disord. 2019 Dec;69:85-90. doi: 10.1016/j.parkreldis.2019.10.015. Epub 2019 Oct 22.