739:, 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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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
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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
405:
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
397:
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.
385:
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
746:
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.
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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.
581:, 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.
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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
771:
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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.
542:, 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
802:
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).
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fluctuations"(Segawa, 2000). Yet some people with dopamine-responsive dystonia do not experience such diurnal fluctuations, causing many researchers to prefer other disease terms.
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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
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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.
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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
477:
303:, 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
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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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626:(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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903:"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
851:"Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency"
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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).
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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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The disease is named after Dr. Masaya Segawa, who provided an early clinical description in 1976.
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804:"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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728:, 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
566:. Not all patients show mutations in the GCH1 gene (
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901:Pitton, Jamir; Caprara, AnaLetícia Fornari (2021).
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Autosomal recessive GTP cyclohydrolase I deficiency
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Characteristic symptoms are increased muscle tone (
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140:. Unsourced material may be challenged and removed.
472:Autosomal dominant GTP cyclohydrolase I deficiency
616:pantothenate kinase-associated neurodegeneration
307:. The disorder responds well to treatment with
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489:6-Pyruvoyltetrahydropterin synthase deficiency
599:), decreased twitching may be noticed during
8:
732:, as well as a biological precursor of the
353:. Unsourced material may be challenged and
61:Learn how and when to remove these messages
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570:), which makes genetic testing imperfect.
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83:needs attention from an expert in medicine
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459:forms of the disease have been reported.
373:Learn how and when to remove this message
218:Learn how and when to remove this message
200:Learn how and when to remove this message
651:primarily dystonic juvenile parkinsonism
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93:may be able to help recruit an expert.
671:dyspeptic dystonia with hiatal hernia
633:include metabolic disorders (such as
499:Dihydropteridine reductase deficiency
485:(autosomal recessive Segawa syndrome)
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474:(autosomal dominant Segawa syndrome)
351:adding citations to reliable sources
138:adding citations to reliable sources
659:early onset idiopathic parkinsonism
390:(both motor and mental skills) and
584:In approximately half of cases, a
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42:This article has multiple issues.
494:Sepiapterin reductase deficiency
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483:Tyrosine hydroxylase deficiency
125:needs additional citations for
50:or discuss these issues on the
149:"Dopamine-responsive dystonia"
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667:dystonia musculorum deformans
394:in the absence of treatment.
624:positron emission tomography
420:Other symptoms - handwriting
267:Dopamine-responsive dystonia
236:Dopamine-responsive dystonia
538:, which encodes the enzyme
85:. The specific problem is:
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920:10.4103/ijmbs.ijmbs_23_21
534:. A mutation in the gene
410:Other symptoms - footwear
388:developmental milestones
707:Diagnosis - additional
631:differential diagnoses
595:During a sleep study (
515:, is synthesised from
966:Advances in Neurology
548:nigrostriatal pathway
504:The precursor of the
301:Parkinsonian features
1126:Congenital disorders
568:GTP cyclohydrolase I
544:tyrosine hydroxylase
540:GTP cyclohydrolase I
524:tyrosine hydroxylase
347:improve this section
134:improve this article
91:WikiProject Medicine
87:almost zero sources.
869:10.3390/jpm11111186
622:of the brain using
528:tetrahydrobiopterin
457:autosomal recessive
400:Parkinson's disease
1066:External resources
951:"Patient registry"
808:Movement Disorders
635:GM2 gangliosidosis
453:Autosomal dominant
315:Signs and symptoms
1102:"Segawa Syndrome"
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820:10.1002/mds.28874
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677:Diagnosis - main
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132:Please help
127:verification
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530:(BH4) as a
241:Other names
1115:Categories
972:: 215–33.
786:References
590:amino acid
295:, such as
160:newspapers
47:improve it
1080:neuro/168
1075:eMedicine
937:233248371
929:1947-489X
913:(1): 44.
836:245260405
720:Treatment
601:REM sleep
579:neopterin
575:biopterin
555:Diagnosis
461:Mutations
334:does not
255:Neurology
250:Specialty
53:talk page
1121:Dystonia
888:34834538
828:34908184
765:Research
737:dopamine
726:levodopa
608:MRI scan
532:cofactor
517:tyrosine
509:dopamine
463:in five
448:Genetics
309:levodopa
297:clubfoot
293:dystonia
281:), is a
1056:C538007
879:8625014
778:History
689:(day2).
519:by the
355:removed
340:sources
283:genetic
174:scholar
1045:600225
978:945938
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693:limbs.
629:Other
521:enzyme
513:L-dopa
299:) and
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147:
1034:G24.1
933:S2CID
832:S2CID
465:genes
181:JSTOR
167:books
1051:MeSH
1040:OMIM
974:PMID
925:ISSN
884:PMID
824:PMID
669:and
577:and
536:GCH1
455:and
338:any
336:cite
153:news
1025:ICD
915:doi
874:PMC
864:doi
816:doi
618:).
614:or
606:An
349:by
271:DRD
136:by
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794:^
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673:.
665:,
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649:)
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279:SS
257:,
56:.
1104:.
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1017:D
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