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)

A deficiency of dihydrobiopterin synthesis was found in a 27-year-old man with mild mental retardation, rigid spasticity, hyperreflexia, dystonia, myoclonus, and delay in the initiation of action, since age 10. Symptoms improved after sleep. Urine contained large amounts of neopterin and a trace of biopterin. Dihydropteridine reductase activity in red blood cells was normal. CSF levels of HVA and 5-HIAA were low. Tetrahydrobiopterin administration lowered serum phenylalanine and improved the symptoms.
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PMID:Dihydrobiopterin synthesis defect: an adult with diurnal fluctuation of symptoms. 243 82

We administered tetrahydrobiopterin (BH4) to 4 patients with progressive dystonia with diurnal variation (PDDV). One patient improved clinically. Deficient CSF concentrations of HVA and 5-HIAA were unchanged despite marked elevation of CSF biopterin concentration. Variable effectiveness of BH4 in PDDV may reflect reduced number or function of biopterin-metabolizing neurons or variable entry of BH4 into these neurons.
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PMID:Tetrahydrobiopterin administration in biopterin-deficient progressive dystonia with diurnal variation. 247 72

Alternating hemiplegia in childhood (Verret, 1971) is a disorder presenting with frequent episodes of alternating hemiplegia from early infancy. We report a patient with this disorder, along with a pathophysiological study and a discussion about the available therapies for this disorder. The patient, an 11-year-old boy, visited our hospital with episodes of alternating hemiplegia from early infancy. His family history showed that many members suffered from migraine. He was born with asphyxia. Mental and motor developmental delays were seen from early infancy. The hemiplegic episodes with ipsilateral facial palsy had occurred frequently from early infancy. The episodes were frequently induced by emotional stress. The duration of hemiplegia varied from 10 minutes to 3 days. From the age of 11 years, he had begun to have migrainous attacks with or without hemiplegic episodes. Neurological examination revealed slight muscle hypotonia, choreoathetosis and dystonic movements induced by locomotion, positive Myerson sign, increased deep tendon reflexes and Babinski reflex. CAG, VAG and CAT revealed normal findings. EEG revealed diffuse generalized slowing during hemiplegic episodes. Measurement of regional cerebral blood flow (CBF) by 133Xe inhalation method revealed a slight decrease of bilateral CBF during a quadriplegic episode. Positron emission tomography using C15O2 revealed a slight decrease of CBF at the insula, putamen and claustrum of the left side during a right sided episode. Increased excretion of urinary 5-HIAA was seen during one episode. From our clinical and laboratory findings, we think this disorder may be a special type of migraine. Therapeutic trials of diazepam and flunarizine were both effective, but the initial effectiveness was decreased after 5 months.
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PMID:[A patient with alternating hemiplegia in childhood]. 273 28

HVA and 5-HIAA in CSF were determined in five patients with non-fluctuating progressive dystonia before and after treatment with L-Dopa. The response to L-Dopa was unequivocally favourable in one patient. The HVA-level in her CSF was significantly reduced before treatment, whereas in the other four non-responding patients the pre-treatment HVA was normal. It is postulated, that the biochemical delineation of clinical responsiveness to a neurotransmitter may provide useful clues towards the classification of extrapyramidal disease in childhood.
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PMID:Treatment of non-fluctuating progressive dystonia: a neuropharmacological approach. 620 4

We studied a patient with action-induced rhythmic dystonia that followed a stroke. Postmortem studies showed an infarct in the right posterolateral ventral part of the thalamus. Electrophysiologic analysis indicated that the eliciting factor of the involuntary movement was an impulse, promoting voluntary contraction of muscle. CSF 5-HIAA content was low, and HVA was high. Administration of 5-HTP and clonazepam abolished the involuntary movements.
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PMID:Action-induced rhythmic dystonia: an autopsy case. 660 63

A 35-year-old female was reported who presented early onset and slowly progressive ataxia and retrocollis which appeared at the age of nine. On admission, neurological examination revealed cerebellar ataxia, dystonia of the neck and the right arm, myoclonus of the neck and the shoulder, slight mental retardation, supranuclear upper gaze palsy, and sensorineural hearing loss. Laboratory examination showed high serum CK activity. Electromyography and muscle biopsy findings suggested slight muscular involvement. CSF level of HVA and 5-HIAA were reduced. MRI demonstrated marked cerebellar atrophy and slight atrophy of the brain stem. To our knowledge, the characteristic combination of the neurological sign in this case has not been reported. This case was compared with EOCA (early onset cerebellar ataxia with retained tendon reflexes) and other juvenile onset cerebellar ataxia and dystonia.
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PMID:[A case of juvenile onset ataxia with dystonia, myoclonus, sensorineural hearing loss and mental retardation]. 826 7

While several radiological findings point towards the basal ganglia as a possible anatomical site of the lesion in dystonia patients the biochemical basis of the disorder is still unknown. 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels-the respective metabolites of serotonin and dopamine-were measured in lumbar cerebrospinal fluid (lCSF) of 15 patients with idiopathic adult-onset focal dystonia and in lCSF of 11 controls. 100 microliters lCSF were analyzed for 5-HIAA and HVA by reversed-phase HPLC with electrochemical detection. 5-HIAA levels were significantly reduced in dystonia patients (11.4 micrograms/ml) compared to controls (18.4 ng/ml) (p < 0.02). HVA levels in dystonia patients (30.3 ng/ml) were below control values (41.6 ng/ml) but this finding did not reach statistical significance. Decreased lCSF levels of 5-HIAA suggest an impaired serotonin metabolism in patients with idiopathic adult-onset dystonia. This observation may provide a biochemical basis for a more specific pharmacotherapy in dystonia patients.
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PMID:Neurotransmitters in CSF of idiopathic adult-onset dystonia: reduced 5-HIAA levels as evidence of impaired serotonergic metabolism. 901 96

Aromatic l-aminoacid decarboxylase (AADC) deficiency is a neurotransmitter defect leading to a combined deficiency of catecholamines and serotonin. Patients are usually detected in infancy due to developmental delay, hypotonia, and extrapyramidal movements. Diagnosis is based on an abnormal neurotransmitter metabolite profile in CSF and reduced AADC activity in plasma. An elevation of vanillactic acid (VLA) has been described as the only abnormality detected in organic acid analysis (OA) of urine. We report a patient who presented in the neonatal period with lethargy, hypotonia, metabolic acidosis, and hypoglycemia. Blood ammonia, lactic acid, and acylcarnitines were normal, but OA of a urine sample showed a small increase of VLA, raising the suspicion of AADC deficiency. The patient was lost to follow-up until the age of 8 months, when he presented with dystonia, abnormal movements, oculogyric crises, and hypothermia. Repeat OA showed not only increased levels of VLA, but also increased vanilpyruvic acid (VPA), N-acetyl-vanilalanine (AVA) and N-acetyl-tyrosine (NAT). Neurotransmitter analysis in CSF showed increased vanilalanine (1200 nmol/L, ref<100) with decreased levels of 5-hydroxy-indoleacetic acid (5-HIAA, < 5 nmol/L; ref 152-462), homovanillic acid (HVA, 83 nmol/L; ref 302-845), and methoxy-hydroxy-phenyl-glycol (<5 nmol/L; ref 51-112). AADC activity in plasma was nearly undetectable. In the urine, low excretion of vanilmandelic acid (<0.3 micromol/mmol creat; ref 0.3-20) and 5-HIAA (0.9 micromol/mmol creat; ref 4-18), was found, but HVA was normal and dopamine even elevated. This contradictory phenomenon of hyperdopaminuria has been described earlier in AADC deficient patients. We postulate that VPA and AVA could originate from vanilalanine (through a transaminase and an acetylase respectively), while NAT could originate from tyrosine through an AA acetylase. This report expands the clinical presentation of AADC deficiency and adds new markers of the disease for OA analysis, improving detection of AADC deficient patients in general metabolic screening procedures.
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PMID:Aromatic l-aminoacid decarboxylase deficiency: unusual neonatal presentation and additional findings in organic acid analysis. 1628 91

Disruption of monoamines metabolism leads to diverse manifestations, including developmental, movement and respiratory dysfunctions. We aimed to correlate clinical phenotypes of 55 children with neurodevelopmental disorders with dopamine (HVA) and serotonin (5-HIIA) metabolites in CSF. Decreased level of at least one metabolite was documented in 49.1% patients. Both metabolites were significantly lower in progressive disorder and extrapyramidal syndrome (p<0.05). HVA was significantly lower in hypokinetic and regulatory disorders (p<0.05). In univariate analysis, only progressive course, extrapyramidal syndrome and dystonia were significantly associated with decreased 5-HIAA. In multivariate regression only progressive course remained significant (p=0.005). Progressive disease, extrapyramidal syndrome, dystonia, tremor and rigidity were positively associated with low HVA. In multivariate analysis only: progressive course and rigidity remained significant. Progressive/rigid phenotype carries a high risk of monoamines deficiency, strongly implying need for their analysis. Psychomotor delay with epilepsy and hypotonia is rarely linked to low monoamines level. Irrespective of final diagnosis, different clinical presentations may be associated with impaired monoamines turnover.
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PMID:Phenotypic features of children with neurodevelopmental diseases in relation to biogenic amines. 2551 85