728:, a neurotransmitter. (Neurotransmitters are naturally produced molecules that may be sequestered following the propagation of an action potential down a nerve towards the axon terminal, which in turn may cross the synaptic junction between neurons, enabling neurons to communicate in a variety of ways.) Low-dose L-dopa usually results in near-complete or total reversal of all associated symptoms for these patients. In addition, the effectiveness of such therapy is typically long term, without the complications that often occur for those with Parkinson's disease who undergo L-dopa treatment. Thus, most experts indicate that this disorder is most appropriately known as dopa-responsive dystonia.
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105:
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No data are available on mortality associated with dopamine-responsive dystonia, but patients surviving beyond the fifth decade with treatment have been reported. However, in severe, early autosomal recessive forms of the disease, patients have been known to pass away during childhood. Girls seem to
758:
Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic
394:
Many patients experience improvement with sleep, are relatively free of symptoms in the morning, and develop increasingly severe symptoms as the day progresses (i.e., diurnal fluctuation). Accordingly, this disorder has sometimes been referred to as "progressive hereditary dystonia with diurnal
386:
In addition, dopamine-responsive dystonia is typically characterized by signs of parkinsonism that may be relatively subtle. Such signs may include slowness of movement (bradykinesia), tremors, stiffness and resistance to movement (rigidity), balance difficulties, and postural instability.
374:
The disease typically starts in one limb, typically one leg. Progressive dystonia results in clubfoot and tiptoe walking. The symptoms can spread to all four limbs around age 18, after which progression slows and eventually symptoms reach a plateau. There can be regression in
735:
Due to commonly being misdiagnosed, it is common for the disease to remain untreated. When left untreated, patients often need
Achilles' tendon surgery by the age of 21. They will also struggle with walking, an ability that will degrade throughout the day.
643:
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This condition is very rare, only affecting one in two million people. It is more common in females than in males. There are several hundred cases in the United States, 25 known cases in the United
Kingdom, and less than that in Australia and New Zealand.
570:, which can help determine the exact form of dopamine-responsive movement disorder: early onset parkinsonism (reduced biopterin and normal neopterin), GTP cyclohydrolase I deficiency (both decreased) and tyrosine hydroxylase deficiency (both normal).
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can provide temporary relief in untreated patients. It also impairs development into adulthood, reduces balance, and reduces calf muscle development. Socially, it can result in depression, lack of social skills, and inability to find employment.
681:
patient with suspected dopamine-responsive dystonia required to walk in around hospital in front of Neuro'-consultant at selected daytime intervals to observe worsening walking pattern coincident with increased muscle tension in
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correct diagnosis only made by a consultant neurologist with a complete 24-hour day-cycle observation (with video/film) at a hospital, i.e., morning (day1)->noon->afternoon->evening->late-night->sleep->morning
1013:
539:
normally peaks during the morning and also decreases with age until after age 20, which explains why the symptoms worsen during the course of the day and with increasing age until the third decade of life.
531:, disrupts the production of BH4, decreasing dopamine levels (hypodopaminergia). This autosomal-dominant condition is the most frequent cause of dopamine-responsive dystonia. Mutations in the gene for
639:
647:
791:
Weissbach A, Pauly MG, Herzog R, Hahn L, Halmans S, Hamami F, Bolte C, Camargos S, Jeon B, Kurian MA, Opladen T, Brüggemann N, Huppertz HJ, König IR, Klein C, Lohmann K (February 2022).
760:
395:
fluctuations"(Segawa, 2000). Yet some people with dopamine-responsive dystonia do not experience such diurnal fluctuations, causing many researchers to prefer other disease terms.
387:
Approximately 25 percent also have abnormally exaggerated reflex responses (hyperreflexia), particularly in the legs. These symptoms can result in a presentation similar to that of
548:
Due to the condition's rarity, it is frequently misdiagnosed, often as cerebral palsy. This results in patients often living their entire childhood with the condition untreated.
535:
may lead to tyrosine hydroxylase deficiency, a rare form of dopamine-responsive dystonia inherited in an autosomal recessive manner. The activity of dopaminergic neurons in the
292:, typically absent in the morning or after rest but worsening during the day and with exertion. Children with dopamine-responsive dystonia are often misdiagnosed as having
688:
diurnal affect of condition: morning (fresh/energetic), lunch (stiff limbs), afternoon (very stiff limbs), evening (limbs worsening), bedtime (limbs near frozen).
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be somewhat more commonly affected. The disease less commonly begins during puberty or after age 20, and very rarely, cases in older adults have been reported.
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have been shown to cause dopamine-responsive dystonia. These mutations, according to a review published in 2021, are associated with the following conditions:
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of the brain can be used to look for conditions that can mimic dopamine-responsive dystonia (for example, metal deposition in the basal ganglia can indicate
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615:(PET scan) shows a normal radiolabelled dopamine uptake in dopamine-responsive dystonia, contrary to the decreased uptake in Parkinson's disease.
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muscle tension in thighs/arms: morning (normal), lunch (abnormal), afternoon (very abnormal), evening (bad), bedtime (frozen solid).
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Segawa M, Hosaka A, Miyagawa F, Nomura Y, Imai H (1976). "Hereditary progressive dystonia with marked diurnal fluctuation".
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near normal handwriting at infants/kindergarten (ages 3–5 school) years (National
Organization for Rare Disorders, 2015).
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The diagnosis of dopamine-responsive dystonia can be made from a typical history, a trial of dopamine medications, and
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49:
41:
892:"Dopa-responsive dystonia: Guanosine triphosphate cyclohydrolase 1, tyrosine hydroxylase, and sepiapterin reductase"
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In those with dopamine-responsive dystonia, symptoms typically dramatically improve with low-dose administration of
343:
840:"Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency"
482:
471:
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126:
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Segawa syndrome, Segawa's disease, Segawa's dystonia, hereditary progressive dystonia with diurnal fluctuation
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Nygaard G, Szigetvar PD, Grindheim AK, Ruoff P, Martinez A, Jaavik J, Kleppe R, Flydal MI (November 2021).
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excessive wear at toes, but little wear on heels, thus replacement of shoes every college term/semester.
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which usually manifests itself during early childhood at around ages 5–8 years (variable start age).
1039:
701:
lack of self-esteem at school/college/university -> eating disorders in youth thus weight gains.
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very hard to diagnose as condition is dynamic w.r.t. time-of-day AND dynamic w.r.t. age of patient.
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324:
771:
The disease is named after Dr. Masaya Segawa, who provided an early clinical description in 1976.
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793:"Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review"
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typically referral by GP to specialist
Neurological Hospital e.g. National Hospital in London.
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worsening pattern of sloppy handwriting best observed by school teachers via termly reports.
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GeneReview/NCBI/NIH/UW entry on GTP Cyclohydrolase 1-Deficient Dopa-Responsive
Dystonia
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and therapeutic strategies a patient registry was established by the noncommercial
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child sufferer displays unhappy childhood facial expressions (possibly depression).
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very bad handwriting (still worsening) during adult (qv post-graduate exams) years.
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lack of energy during late-daytime (teens/adult) -> compensate by over-eating.
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very poor (worse) handwriting during teen (qv GCSE/A level-public exams) years.
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throughout the day, reducing leg-gait, thus shoe heels catching one another.
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bad handwriting (worsening) during post-teen (qv university exams) years.
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Sometimes a lumbar puncture is performed to measure concentrations of
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autosomal recessive early onset parkinsonism with diurnal fluctuation
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717:, which is a biochemically significant metabolite of the amino acid
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International
Working Group on Neurotransmitter Related Disorders
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phenylalanine to tyrosine. This process uses BH4 as a cofactor.
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GeneReview/NCBI/NIH/UW entry on
Tyrosine Hydroxylase Deficiency
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loading test can be used to show decreased conversion from the
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poor handwriting at pre-teens (ages 8–11 school) years.
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Ibnosina
Journal of Medicine and Biomedical Sciences
555:. Not all patients show mutations in the GCH1 gene (
890:Pitton, Jamir; Caprara, AnaLetícia Fornari (2021).
467:
Autosomal recessive GTP cyclohydrolase I deficiency
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Characteristic symptoms are increased muscle tone (
129:. Unsourced material may be challenged and removed.
461:Autosomal dominant GTP cyclohydrolase I deficiency
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605:pantothenate kinase-associated neurodegeneration
296:. The disorder responds well to treatment with
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478:6-Pyruvoyltetrahydropterin synthase deficiency
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588:), decreased twitching may be noticed during
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721:, as well as a biological precursor of the
342:. Unsourced material may be challenged and
50:Learn how and when to remove these messages
559:), which makes genetic testing imperfect.
72:needs attention from an expert in medicine
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448:forms of the disease have been reported.
362:Learn how and when to remove this message
207:Learn how and when to remove this message
189:Learn how and when to remove this message
640:primarily dystonic juvenile parkinsonism
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82:may be able to help recruit an expert.
660:dyspeptic dystonia with hiatal hernia
622:include metabolic disorders (such as
488:Dihydropteridine reductase deficiency
474:(autosomal recessive Segawa syndrome)
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463:(autosomal dominant Segawa syndrome)
340:adding citations to reliable sources
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127:adding citations to reliable sources
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648:early onset idiopathic parkinsonism
379:(both motor and mental skills) and
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573:In approximately half of cases, a
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31:This article has multiple issues.
483:Sepiapterin reductase deficiency
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472:Tyrosine hydroxylase deficiency
114:needs additional citations for
39:or discuss these issues on the
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138:"Dopamine-responsive dystonia"
1:
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656:dystonia musculorum deformans
383:in the absence of treatment.
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613:positron emission tomography
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409:Other symptoms - handwriting
256:Dopamine-responsive dystonia
225:Dopamine-responsive dystonia
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527:, which encodes the enzyme
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74:. The specific problem is:
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909:10.4103/ijmbs.ijmbs_23_21
523:. A mutation in the gene
399:Other symptoms - footwear
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377:developmental milestones
696:Diagnosis - additional
620:differential diagnoses
584:During a sleep study (
504:, is synthesised from
955:Advances in Neurology
537:nigrostriatal pathway
493:The precursor of the
290:Parkinsonian features
1115:Congenital disorders
557:GTP cyclohydrolase I
533:tyrosine hydroxylase
529:GTP cyclohydrolase I
513:tyrosine hydroxylase
336:improve this section
123:improve this article
80:WikiProject Medicine
76:almost zero sources.
858:10.3390/jpm11111186
611:of the brain using
517:tetrahydrobiopterin
446:autosomal recessive
389:Parkinson's disease
1055:External resources
940:"Patient registry"
797:Movement Disorders
624:GM2 gangliosidosis
442:Autosomal dominant
304:Signs and symptoms
1091:"Segawa Syndrome"
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809:10.1002/mds.28874
381:failure to thrive
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666:Diagnosis - main
601:Wilson's disease
495:neurotransmitter
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851:(1186): 1186.
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179:December 2022
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134:Find sources:
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121:Please help
116:verification
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33:Please help
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519:(BH4) as a
230:Other names
1104:Categories
961:: 215–33.
775:References
579:amino acid
284:, such as
149:newspapers
36:improve it
1069:neuro/168
1064:eMedicine
926:233248371
918:1947-489X
902:(1): 44.
825:245260405
709:Treatment
590:REM sleep
568:neopterin
564:biopterin
544:Diagnosis
450:Mutations
323:does not
244:Neurology
239:Specialty
42:talk page
1110:Dystonia
877:34834538
817:34908184
754:Research
726:dopamine
715:levodopa
597:MRI scan
521:cofactor
506:tyrosine
498:dopamine
452:in five
437:Genetics
298:levodopa
286:clubfoot
282:dystonia
270:), is a
1045:C538007
868:8625014
767:History
678:(day2).
508:by the
344:removed
329:sources
272:genetic
163:scholar
1034:600225
967:945938
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924:
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682:limbs.
618:Other
510:enzyme
502:L-dopa
288:) and
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1023:G24.1
922:S2CID
821:S2CID
454:genes
170:JSTOR
156:books
1040:MeSH
1029:OMIM
963:PMID
914:ISSN
873:PMID
813:PMID
658:and
566:and
525:GCH1
444:and
327:any
325:cite
142:news
1014:ICD
904:doi
863:PMC
853:doi
805:doi
607:).
603:or
595:An
338:by
260:DRD
125:by
1106::
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1032::
1021::
1018:10
959:14
957:.
920:.
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842:.
819:.
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801:37
799:.
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783:^
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662:.
654:,
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638:)
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630:,
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592:.
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268:SS
246:,
45:.
1093:.
1016:-
1006:D
969:.
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