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 report on two cases of children suffering from biopterin synthetase deficiency. Both were treated with the same treatment schedule with biopterin and neurotransmitters: 6-hydroxytryptophan and dihydrophenylalanine (DOPA). The only difference between the two cases is the time of diagnosis and therefore of treatment. The child who was treated early has a normal neurologic development. The other one has been treated since he was 7 months old and is mentally deficient (DQ = 0.60). This older child also suffers from dystonia probably secondary to Levodopa treatment. The authors emphasize the uncertainty of these patient's evolution owing to complications of the disease itself or those due to prolonged treatment by neurotransmitters.
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PMID:[Diagnosis of deficiency in cofactor of phenylalanine hydroxylase: a metabolic emergency]. 251 61

A daughter and her mother developed hereditary progressive dystonia with marked diurnal fluctuation (HPD) at the age of 4 and 34, respectively. L-Dopa, tetrahydrobiopterin (BH4) or 5-hydroxytryptophan (5-HTP) was orally administered to them. L-Dopa cured completely their symptoms. 5-HTP as well as BH4 improved their symptoms, especially dystonic movements. Biopterin and 5-hydroxyindoleacetic acid concentrations in CSF increased during BH4 medication. These findings suggest that the serotonergic system of the central nervous system might play some role in the pathogenesis of dystonia in HPD.
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PMID:Effect of tetrahydrobiopterin and 5-hydroxytryptophan on hereditary progressive dystonia with marked diurnal fluctuation: a suggestion of the serotonergic system involvement. 325 39

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

It is evident from this review that there is much that we know and much that we still do not know about DRD. In terms of diagnosis and clinical management, there is general agreement that patients with childhood-onset dystonic symptoms of unknown etiology should be treated initially with levodopa with the later addition, if necessary, of other medications (for example, BH4, 5-hydroxytryptophan). Although the results of molecular genetic and CSF studies are, at this time, unlikely to significantly alter clinical management of the patient, these analyses could be useful in providing information on prognosis (that is, DRD versus progressive neurodegenerative disorders or more severe metabolic disorders). It is also clear that notwithstanding the discovery of GCH1 and hTH mutations responsible for DRD, there remain many important unresolved issues regarding this disorder, including questions of female predominance, phenotypic heterogeneity, and presence of childhood-onset dystonia versus the expected parkinsonism resulting from a striatal DA deficit. We are confident that answers to these interesting questions on DRD will, in addition to providing clarification of the mechanisms of this disorder, provide exciting information relating to the pathogenesis of other types of dystonia as well as PD and to long-standing issues regarding a role of DA and serotonin in normal human brain development.
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PMID:Dopa-responsive dystonia: recent advances and remaining issues to be addressed. 1049 30

The autosomal recessive mutation dystonia musculorum (dt(J)/dt(J)) causes degenerative alterations of peripheral and central sensory pathways that lead to ataxia. To investigate possible changes in the central serotonin system of these mice, HPLC measurements of 5-hydroxytryptophan, 5-hydroxy-tryptamine (serotonin; 5-HT), and 5-HT metabolites were obtained from 22 brain regions and the spinal cord of wild type and dt(J)/dt(J) mutant mice. Also, 5-HT transporters were quantified by [(3)H]citalopram autoradiography in 72 brain regions, subregions, and nuclei, and the 5-HT innervation visualized by immunocytochemistry throughout the brain and spinal cord. In all brain regions measured for indoleamine content, there were no significant differences between the two genotypes. In the spinal cord, an increased tissue concentration of 5-HT (+34%), 5-hydroxyindole-3-acetic acid (+33%), 5-hydroxytryptophol (+21%), and 5-hydroxytryptophan (+45%) in dt(J)/dt(J) actually corresponded to the same total amount of each of these indoleamines in the entire spinal cord, when taking into account its reduced size in the mutants. Quantification of the binding to 5-HT transporters showed increases in the medial geniculate nucleus (+14%), medial (+24%) and lateral (+18%) hypothalamus, interpeduncular (+13%), vestibular (+22%), and deep cerebellar nuclei (+37%) of dt(J)/dt mice, and decreases in the ventral tegmental area (-13%), median and linear raphe nuclei (-20%), as well as in the solitary complex (-35%). There were no apparent differences in the distribution of 5-HT-immunostained fibers in these and other regions of brain and in the spinal cord of dt(J)/dt(J) compared to wild type mice. The bulk of these results indicates a relative sparing of the central 5-HT system in the dt(J)/dt(J) mice, even though alterations in 5-HT transporters could justify attempts at improving the sensorimotor dysfunction by administration of serotoninergic agents in these mice.
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PMID:Central serotonin system in Dystonia musculorum mutant mice: biochemical, autoradiographic and immunocytochemical data. 1088 Oct 40

We report a case of autosomal dominantly inherited dystonia and panic attacks to discuss successful treatment of a common serotonergic pathology with medication. The objective analysis of the movement disorder was done by Optotrak. First we demonstrate a reduction of the myoclonus by L-5-hydroxytryptophan, which inhibits after 11 months. After changing the medication to Nefadozone, the myoclonus and the frequency of panic attacks were reduced.
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PMID:[Familial myoclonus-dystonia syndrome associated with panic attacks]. 1108 16

Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable by neonatal phenylketonuria screening programs. We describe an 8-year-old girl with delay, seizures, and dystonia with mild hyperphenylalaninemia detected in late childhood. The diagnosis of 6-pyruvoyl-tetrahydrobiopterin synthase deficiency was made by analysis of pterins in urine, pterins and neurotransmitters in cerebrospinal fluid, and enzyme assay. The patient improved clinically taking oral tetrahydrobiopterin, levodopa/carbidopa, and 5-hydroxytryptophan. This treatable condition may not always be detected by routine population screening for hyperphenylalaninemia.
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PMID:6-pyruvoyl-tetrahydropterin synthase deficiency with mild hyperphenylalaninemia. 1598 17

The diagnosis of a 14-year-old girl with a new homoallelic mutation in the sepiapterin reductase (SR) gene is reported. Initially she presented at the age of 2 with hypotonia and mild cognitive developmental delay, and was diagnosed as having mild methylmalonic aciduria, which was recently identified as methylmalonylCoA racemase deficiency, a new defect in valine-isoleucine metabolism. After a 12-year progression of her neurologic condition, which had made her wheelchair-bound at the age of 6, dystonia with diurnal variation had become apparent. At the age of 14 this finding led to rapid diagnosis of SR deficiency. The diagnostic approach with CSF neurotransmitter and pterins analysis and combined phenylalanine/BH(4) loading test, and finally measurement of sepiapterin in CSF is illustrative for the diagnosis of SR deficiency. As in all other patients with this new defect, very low levels of homovanillic acid and 5-hydroxyindoleacetic acid and high levels of biopterin and sepiapterin in the CSF are the diagnostic hallmark. The girl improved dramatically on treatment with L-DOPA and 5-hydroxytryptophan. The initial diagnosis of methylmalonic aciduria may afterwards be considered to have not significantly contributed to her clinical condition and only has led to a long delay of the clinically relevant diagnosis of SR deficiency. Although the clinical condition of this recently recognized autosomal recessive defect in pterin metabolism is complex and many symptoms can occur in variable severity and time of onset, dystonia with diurnal variation is a characteristic finding, as shown in nearly all patients described so far. The rapid and favourable response on treatment with L-DOPA warrants the classification of SR deficiency as another autosomal recessive type of DOPA-responsive dystonia (DRD). This classification is important to improve the awareness of clinicians that more than one metabolic defect can underlie the phenotype of a DOPA-responsive dystonic disorder and that dystonia should always trigger a rapid diagnosis of the underlying neurotransmitter synthesis defect, in view of the excellent treatability of a DRD.
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PMID:Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia. 1665 Jul 84

We describe a unique presentation of autosomal recessive (AR) GTP cyclohydrolase I (GTPCH) deficiency, with severe CNS involvement but without hyperphenylalaninemia. A male infant presented with progressive spasticity, dystonia and oculogyric episodes. Blood phenylalanine levels were persistently normal: whereas an oral phenylalanine loading test revealed impaired phenylalanine clearance. CSF neopterin and tetrahydrobiopterin (BH(4)) were low, homovanillic acid marginally low and 5-hydroxyindoleacetic acid normal. Fibroblasts showed decreased GTPCH enzyme activity. A homozygous novel mutation of GCH1, p.V206A, was identified. On treatment (BH(4), L-Dopa/Carbidopa and 5-hydroxytryptophan), motor development improved. Mutational analysis provided neonatal diagnosis of a younger brother who, after 18 months on treatment, shows normal development. AR GTPCH I deficiency can present without hyperphenylalaninemia and with normal or subtle CSF neurotransmitter profiles. Testing for GTPCH deficiency should be considered for patients with unexplained neurological symptoms and extrapyramidal movement disorder.
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PMID:Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms. 1827 79

Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inheritance in Man #128230). DRD is a genetically heterogeneous and clinically complex movement disorder that is usually treated with l-dopa, a precursor of the neurotransmitter dopamine. Whole-genome sequencing identified compound heterozygous mutations in the SPR gene encoding sepiapterin reductase. Disruption of SPR causes a decrease in tetrahydrobiopterin, a cofactor required for the hydroxylase enzymes that synthesize the neurotransmitters dopamine and serotonin. Supplementation of l-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.
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PMID:Whole-genome sequencing for optimized patient management. 2167


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