Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the clinical features of parkinsonism in 25 patients whose age of onset was under 40 years. Among them, 17 patients, whose age of onset was after their 21st birthday, were classified as young onset Parkinson's disease (YOPD), and the remaining 8 whose age of onset was before their 21st birthday were classified as juvenile parkinsonism (JP). Rigidity and akinesia were revealed in all 25 patients. Resting tremor was observed in only 5 patients; 3 in the YOPD group and 2 in the JP group. There were 8 of the 25 patients (32%) who experienced an aching sensation in the leg before or at the onset of the parkinsonian features. In 6 of these 8 cases, the sensory symptoms were on the same side where the clinical manifestations of parkinsonism later developed. In the JP group, 2 patients had right foot dystonia, which improved with levodopa. Diurnal fluctuations in parkinsonian symptoms were found in 9 of the 25 cases. The familial incidence of parkinsonism was higher in the JP group. The parkinsonian disabilities in all 25 cases responded dramatically to levodopa therapy. Unfortunately, 10 cases, 5 in the YOPD group and 5 in the JP group, developed dyskinesia. The longer they took levodopa, the greater the chance of developing dyskinesia. The cumulative percentage of dyskinesia was 100% in the YOPD group and 83% in the JP group by the seventh and fourth year of treatment, respectively. A positive correlation was found between the prevalence of dyskinesia and the duration of treatment in both groups.
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PMID:Early onset parkinsonism in Chinese. 168 78

Progressive dystonia with diurnal fluctuations sensitive to levodopa, also known as Segawa's disease, is a rare form of autosomal dominant extrapyramidal disease in the pediatric age group. The dystonic and Parkinson-like symptoms are the main clinical features of the disease and, characteristically but not in all cases, show a diurnal variation. They are absent or present to a lesser extent in the morning, worsening during the day. Treatment with small doses of levodopa results in remission or marked improvement of the symptomatology. We present the case of a 11 years old female patient that developed a dystonic posture in her feet that led her to a tip-toe walking pattern, since the age of 2. Diurnal fluctuations of the symptomatology were noticed by her mother. At 7 years of age she developed a left deviation of the head and an abnormal flexor posture of the left arm. In the next years the symptoms progressed and the fluctuations became less evident. At the age of 10, they were present soon after she woke up in the morning. The neurological examination disclosed a dystonic posturing of the head and left arm, a generalized rigidity of the extremities and a palpebral tremor. Laboratory examinations, including copper and ceruloplasmin, and neuro-imaging studies were negative. She was started on levodopa 150 mg/day with prompt disappearance of the symptomatology. After one-year follow-up she is symptom-free with only 100 mg/day of levodopa. No adverse effect was observed so far.
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PMID:DOPA-sensitive progressive dystonia of childhood with diurnal fluctuations of symptoms: a case report. 748 43

We report the clinical features of four female patients with dopa-responsive dystonia (DRD), and the survey of the family members. The patients were 2 sisters and 2 sporadic patients from 3 families. Their age of onset ranged between 5 and 13 years. The clinical manifestation was characterized by limb dystonia which was relieved by L-dopa treatment. Diurnal fluctuation disappeared 15 years later in one patient. There was a wide spectrum of Parkinsonian features and variability of dystonia. Response of L-dopa was still excellent 20 years later. In survey of the family members, there was neither bradykinesia, rigidity, tremor nor dystonia.
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PMID:Dopa-responsive dystonia: clinical and family study in Taiwanese. 868 79

A 14-year-old girl with Segawa disease is reported. The dystonic movement began at the age of three and slow progressive deterioration followed. The girl became bed-ridden and required assistance for all activities of daily living. Diurnal fluctuation and sleep benefit was clearly observed. Inheritence appears to be autosomal dominant. A dramatic, immediate and sustained response to L-dopa therapy was noted. This disorder is a form of treatable dystonia in childhood and adolescence and it is recommended that patients in this age group with primary dystonia should be given a trial of low dose L-dopa even though they have a chronic course or severe disability.
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PMID:Segawa disease. 885 28

Among heterogeneous diseases manifested by parkinsonism beginning early in life, there is a disease presenting with marked diurnal fluctuation of symptoms, called autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF). To identify the characteristics of this condition as a disease entity, we examined the clinical manifestations of AR-EPDF patients (Group I, n = 42) in comparison with those of early-onset parkinsonism patients without diurnal fluctuation (Group II, n = 34). Family history suggesting autosomal recessive inheritance was noted in 85.7% of Group I patients and 17.6% of Group II. The male-to-female ratio was 1: 1.8 in Group I, and 1:0.89 in Group II. Age at onset showed a standard distribution with an average of 25.6 years (SD: +/- 7.7) in Group I and an average of 32.7 with an increasing pattern toward 40 years in Group II. The initial symptom was dystonic gait disturbance in 42.9% of Group I and 5.9% of Group II, parkinsonian gait in 19.9% of Group I and 2.9% of Group II, and tremor in 28.6% of Group I and 41.2% of Group II. The main clinical feature was parkinsonism in both groups. Diurnal fluctuation of parkinsonism was remarkable in all but one (97.6%) of Group I, while it was not observed in Group II. Dystonic postures were noted in 79.4% of Group I and in 37.1% of Group II; hyperactive tendon reflexes in 74.3% of Group I patients and in 20% of Group II. Autonomic symptoms were mild in both groups. None of the Group I patients had dementia while two of Group II did. Levodopa was markedly effective in both groups. Dopa-induced dyskinesia was observed in 96.8% of Group I and in 61.8% of Group II. As for progression of the disease, the Hoehn-Yahr stage of patients on medication was evaluated as 2.2 +/- 0.7 (mean +/- SD) in Group I and 3.1 +/- 1.1 in Group II for a period of 10 to 20 years of onset, 2.5 +/- 0.8 in Group I and 3.3 +/- 0.5 in Group II for 20 to 30 years, and 3.2 +/- 0.9 in Group I and 4.3 +/- 0.6 in Group II after 30 years. There were significant differences between the two groups in the frequency of positive family history, in the mean and distribution of age at onset, in the incidence of dystonic gait as the initial symptom, and in the incidences and medians of the variables including dystonia, hyperreflexia and dopa-induced dyskinesia, as well as in the progression of the disease. Thus, we have successfully characterized the clinical features of AR-EPDF and demonstrated that diurnal fluctuation is a cardinal symptom of this disease. Reported pathologic studies on AR-EPDF showed the nigral lesion characterized by non-Lewy body type degeneration and the occurrence of melanin-poor neurons. These pathologic findings as well as the clinical manifestations differentiate AR-EPDF from Parkinson's disease and from autosomal-dominant familial parkinsonism. Low melanin-content of the nigral neurons is also a striking feature of hereditary progressive dystonia with diurnal fluctuation, in which unlike AR-EPDF there is no neuronal loss in the substantia nigra.
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PMID:[Autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF)--clinical characteristics]. 895 46

Segawa disease (hereditary progressive dystonia with marked diurnal fluctuation) is an autosomal dominant, childhood onset, postural dystonia and the first hereditary basal ganglia disorder whose causative enzyme and gene defect were clarified. The initial symptom is unilateral pes equinovarus with marked diurnal fluctuation. Progression becomes slower after mid-teens and stationary after thirties. Postural tremor may occur after 10 years of age, especially after thirties. Parkinsonian resting tremor action and torsion dystonia. and disturbed locomotion do not occur. L-Dopa shows marked and sustained effect without side effects. F-Dopa PET and [11C] raclopride PET of over 20-year-old cases are normal. Deficiency of GTP cyclohydrolase I (GCH-I) was suggested from low CSF biopterin and neopterin. Mutation of GCH-I gene and decreased GCH-I were clarified as etiology. Twenty-five mutations discordant among families have been found. Autopsy of a gene proven case revealed decreased striatal tyrosine hydroxylase (TH) and dopamine (DA) in ventral striatum where direct pathway is predominant. Decreased GCH-I causes decreased tetrahydrobiopterin (BH4), TH and DA in nigrostriatal (NS) terminal. The lowest affinity of BH4 to TH causes selective involvement of DA. Postural dystonia is caused by decreased TH and DA affecting D1-direct pathway. Thalamic ventrolateral and pedunculo-pontine nuclei are spared. Diurnal fluctuation of symptoms is due to diurnal fluctuation of TH and DA at NS-DA terminal. Decreased DA to below 20% of normal, shown by polysomnographical studies, and its physiological age related decremental changes in NS-DA terminal underlies characteristic clinical course. High D2 receptor before early thirties masks D1 related hypertonus and manifest progression before 20 years of age. Other pteridine abnormalities also cause dopa responsive postural dystonia with diurnal fluctuation. A case of juvenile parkinsonism without dystonia showed decreased TH in dorsolateral putamen where indirect pathway is predominant. These suggest that decreased TH due to decreased BH4 involves D1-direct pathway causing dystonia, and decreased TH itself involves D2-indirect pathway causing parkinsonism.
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PMID:[Segawa disease]. 957 70

Authors present 6 cases of dopa responsive dystonia (DRD) with delayed diagnosis. DRD was firstly described by Segawa et al. in 1976, but in 90's its genetic linkage to chromosomes 14 and 11 was proven. It resulted in possible effective treatment (substitution with low dosages of levodopa). Nevertheless, the correct diagnosis is difficult. DRD usually starts as a foot dystonia with gait difficulties and subsequent overflow of dystonic movements to other muscles and parts of the body, with parkinsonian features and pyramidal signs in part of cases. Diurnal fluctuations with deterioration in the evening are typical for DRD. Dystonia starting in lower extremities may be misdiagnosed with cerebral palsy, what may have consequences in surgical interventions (as in our two cases). Authors present diagnostic difficulties in 6 cases with diagnosis made after 5 to almost 30 years after onset of symptoms and with several surgical interventions performed in 2 cases. The trial with levodopa is crucial for diagnosis and treatment, because low dosages are effective and there are no typical for juvenile parkinsonism treatment complications as dyskinesias and/or fluctuations. The take home message from literature and presented material should be not age dependent clinical trial with levodopa therapy in all cases of dystonia starting in extremities.
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PMID:[Dopa-responsive dystonia (Segawa variant): clinical analysis of 7 cases with delayed diagnosis]. 1509 38

This study presents the clinical findings on seven children from Malta (population 385,000). All of them had early motor delay and a significant degree of cognitive impairment. Diurnal variation of the motor impairments was clear in six out of seven of the subjects and oculogyric crises occurred from an early stage also in six out of the seven. Five out of seven had clear evidence of dystonia but the early picture was dominated by hypotonia in five. Two had early Parkinsonian tremor and chorea was seen in four, although in two this was attributable to the use of L-dopa. Three had early bulbar involvement. In all, although minor motor problems persisted, the response to L-dopa was dramatic and there was a need to balance improvement in dystonia against aggravation of chorea. The majority were not able to walk until they were treated. Increased doses of L-dopa were required in hot weather, to which they were sensitive. Despite a good response of improved motor ability and abolition of oculogyric crises, there was no obvious change in cognitive function with learning remaining in the moderate impairment range. This report widens the phenotype of dopa-responsive motor disorders and the range of young children with primary motor delay (cerebral palsy) who need a clinical trial of L-dopa. All of the subjects had the same novel mutation in the tetrahydrobiopterin pathway involving sepiapterin reductase, and no abnormality in the gene encoding guanosine triphosphate cyclohydrolase 1. Clinically and molecularly the condition shows autosomal recessive inheritance.
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PMID:Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder. 1604 44

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a dopa-responsive dystonia, now called autosomal dominant GTP cyclohydrolase 1 deficiency or Segawa disease, caused by mutation of the GCH-1 gene located on 14q22.1 to q22.2. Because of heterozygous mutation, partial deficiency of tetrahydrobiopterin affects tyrosine hydroxylase (TH) rather selectively and causes decrease of TH in the terminals of the nigrostriatal dopamine (NS DA) neurons, projecting to the D1 receptors on the striosome, the striatal direct pathways and the subthalamic nucleus (STN) and the D4 receptors of the tuberoinfundibular tract. The activities of TH in the terminal are high in early childhood decrease exponentially to the stational level around early twenties, and show circadian oscillatron. TH in HPD follows these variations with around 20% of normal levels and with development of the downstream structures show appears characteristic clinical symptoms age dependently. In late fetus period to early infancy, through the striosome-substantia nigra pars compacta pathway failure in morphogenesis of the DA neurons in substantia nigra, in childhood around 6 years postural dystonia through the D1 direct pathways and the descending output of the basal ganglia. Diurnal fluctuation is apparent in childhood but decrease its grade with age. TH deficiency at the terminal on the STN causes action dystonia from around 8 years and postural tremor from around 10 years, focal dystonia in adulthood. Adult onset cases in the family with action dystonia start with writer's cramp, torticollis or generalized rigid hypertonus with tremor but do not show postural dystonia. TH deficiency on the D4 receptors causes stagnation of the body length in childhood. With or without action dystonia depends on the locus of mutation. Postural dystonia is inhibitory disorder, while action dystonia is excitatory disorder. The TH deficiency at the terminal does not cause morphological changes or degenerative process. Thus, levodopa shows favorable effects without any relation to the duration of illness.
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PMID:Hereditary progressive dystonia with marked diurnal fluctuation. 2109 87