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)

In 1960, progressive sensorineural deafness (McKusick 304,700, DFN-1) was shown to be X-linked based on a description of a large Norwegian pedigree. More recently, it was shown that this original DFN-1 family represented a new type of recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. This new disorder, termed Mohr-Tranebjaerg syndrome (referred to here as DFN-1/MTS) was mapped to the Xq21.3-Xq22 region2. Using positional information from a patient with a 21-kb deletion in chromosome Xq22 and sensorineural deafness along with dystonia, we characterized a novel transcript lying within the deletion as a candidate for this complex syndrome. We now report small deletions in this candidate gene in the original DFN-1/MTS family, and in a family with deafness, dystonia and mental deficiency but not blindness. This gene, named DDP (deafness/ dystonia peptide), shows high levels of expression in fetal and adult brain. The DDP protein demonstrates striking similarity to a predicted Schizosaccharomyces pombe protein of no known function. Thus, is it likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurological development.
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PMID:A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness. 884 Nov 89

A family with a newly detected X-linked syndrome including sensorineural deafness, mental retardation, dystonia and blindness was examined with full-field electroretinography in order to order to find out if the blindness was caused by a retinal degeneration. Six affected males and 2 obligate carriers showed no signs of retinal degeneration. One of 7 affected males had central areolar choroidal dystrophy confirmed by central scotomas in visual fields and an electroretinographic pattern consisting of an attenuated amplitude as well as a prolonged implicit time of the cone b-wave on stimulation with 30 Hz flickering white light.
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PMID:Full-field electroretinograms in a family with Mohr-Tranebjaerg syndrome. 901 58

Midazolam has GABAergic effects in children that may modify propofol-induced involuntary movements, yet delay recovery. In a double-blind, randomized study, 24 children (2-7 yr of age, ASA physical status I or II) undergoing short surgical procedures received midazolam 0.5 mg/kg (Group M) or placebo (Group P) per os 20-30 min before propofol anesthesia (5 mg/kg intravenously followed by an infusion). Blind observers scored sedation and anxiety levels (scale 1-4) before premedication, at separation from parents, and at induction of anesthesia. Induction and emergence were videotaped, and body movements were recorded. During recovery, times to eye opening and maximum Steward (SS = 6) and Vancouver Sedative Recovery (VSRS = 22) scores were noted. Parents were questioned about side effects that may have occurred during the following week. Both groups were similar in age, sex, weight, timing of premedication, propofol dose, and duration of surgery. The incidence of involuntary movements did not differ between groups but was higher at induction (79%) than on emergence (25%) (P < 0.05). Anxiety and sedation scores were similar in Group P and Group M, but recovery took longer after midazolam, with eye opening (mean +/- SD) 24 +/- 7 vs 43 +/- 18 min, maximum SS (median and range) 27 (13-37) vs 55 (24-138) min, and maximum VSRS 51 (30-100) vs 80 (50-130) min. Children returned to normal activity in 1 (0-5) day, and none exhibited neurological complications. We conclude that an oral premedicant dose of midazolam prolongs recovery from anesthesia in children without affecting dystonic movements after propofol.
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PMID:Midazolam premedication delays recovery after propofol without modifying involuntary movements. 921 21

The Mohr-Tranebjaerg syndrome (MTS), a neurodegenerative syndrome characterized by progressive sensorineural hearing loss, dystonia, mental retardation and blindness, is a mitochondrial disease caused by mutations in the deafness/dystonia peptide 1 (DDP1) gene. DDP1 shows similarity to the yeast proteins Tim9, Tim10 and Tim12, components of the mitochondrial import machinery for carrier proteins. Here, we show that DDP1 belongs to a large family of evolutionarily conserved proteins. We report the identification, chromosomal localization and expressional analysis of six human family members which represent further candidate genes for neurodegenerative diseases.
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PMID:The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom. 1061 80

Of 51 consecutive children with cerebral malaria, fever, convulsions, and drowsiness were the commonest presenting symptoms. Decerebrate and decorticate postures and absent cornea reflex were the commonest brain stem signs. Opening lumbar cerebrospinal (CSF) pressure was raised in all but one of 24 children in whom it was reliably measured [mean 15.2 +/- 5.7 mmHg, range 6-24]. Hyponatraemia occurred in 17 (33%). Acute renal failure was not uncommon; the combination of hypercreatininaemia (plasma creatinine > 100 mumol/L) and hyperkalaemia (plasma potassium > 6.0 mumol/L) was fatal in 5 out of 7 patients in whom it occurred. Disturbances of acid-base status were present in all 40 children in whom it was assessed on admission. Mortality rate was 16% (8 patients). Neurological deficits occurred in 7 (14%) of the survivors and included cortical blindness [3], aphasia [3], hypertonia [3], hearing loss [2], and dystonia [1]. In addition to the present measures aimed at reducing morbidity and morality in children with cerebral malaria, efforts should be directed at rapid assessment of renal function and prompt correction of such dysfunction if found.
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PMID:Clinical study of cerebral malaria in African children. 1089 20

We report the clinical, biochemical, neuroradiological, and neurophysiological findings of a 4-year-old Chinese girl with infantile isolated sulphite oxidase deficiency. This is the first reported case in our locality. She presented at the age of 5 months with refractory seizures and developmental regression, and progressed rapidly to profound psychomotor retardation, spasticity, dystonia, microcephaly, and blindness. At the age of 3.5 years, she was admitted to the intensive care unit with septic shock. Ophthalmologic examination at this time revealed bilateral dislocation of the lens. Diagnosis of this very rare disorder was made on the basis of increased levels of urinary sulphite, thiosulphate, and sulphocysteine; normal urine xanthine and hypoxanthine; normal plasma uric acid; and low plasma cystine levels. The diagnosis was confirmed by the absence of sulphite oxidase activities in skin fibroblasts. Isolated sulphite oxidase deficiency is a rare inborn error of sulphur metabolism that is difficult to diagnose on clinical features and routine metabolic tests. The presence of ectopia lentis, seizures, and progressive neurological abnormalities should alert clinicians to the diagnosis.
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PMID:Infantile isolated sulphite oxidase deficiency in a Chinese family: a rare neurodegenerative disorder. 1216 32

The Mohr-Tranebjaerg syndrome (MTS) is a rare neurodegenerative disorder characterized by early-onset deafness, dystonia and further neurological abnormalities such as cortical blindness, spasticity, dementia and mental retardation. Causative mutations were identified within the deafness-dystonia peptide (DDP1/TIMM8a) gene on the X-chromosome. The DDP1 protein is located in the intermembrane space of human mitochondria. Here, it acts in a complex together with its partner protein Tim13 in a chaperone-like manner to facilitate the import of nuclear-encoded precursor proteins into the mitochondrial inner membrane. Thus, MTS is a novel type of mitochondrial disorder. To obtain more insight into the pathophysiology of this neurodegenerative disorder, we performed for the first time a comprehensive clinical and functional characterization of a patient suffering from MTS. This patient exhibited a typical combination of deafness, dystonia and visual loss. Sequence analysis of the patient's DDP1 gene revealed a G to C transversion at nucleotide position 38 of the first exon. The mutation affects the ATG start codon, thereby changing methionine to isoleucine (M1I), and leads to a complete absence of the DDP1 protein. In addition, the partner protein Tim13 was found to be significantly reduced, suggesting that Tim13 requires the presence of DDP1 for its stabilization. The assessment of mitochondrial functions showed the enzyme activities of the mitochondrial energy-generating systems to be normal in the muscle biopsy. Structural abnormalities or aggregations of mitochondria were absent. Electron microscopy revealed only a mild neurogenic atrophy. Neurophysiological investigations showed cochlear dysfunction and disturbance of visual pathways. PET and MRI studies revealed a multifocal pattern of neurodegeneration with hypometabolic areas predominantly located over the right striatum and parietal cortex and marked atrophy of the occipital lobes. Although the visual loss is caused predominantly by neurodegeneration of the visual cortex, degeneration of the retina and the optic nerve contributes to the visual impairment. The pathological changes in basal ganglia and sensory cortex demonstrate the disintegration of subcortico-cortical circuits and correlate well with the clinical presentation of multifocal dystonia. The data presented here showed that, in contrast to most of the known mitochondrial disorders, MTS appears not to be associated with a functional defect of the energy generation system of the mitochondria. Whereas the specific mitochondrial dysfunction leading to neuronal loss in MTS remains to be clarified, the electrophysiological and neuroimaging findings allowed the multifocal manifestation of neurodegenerative lesions in MTS to be characterized specifically.
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PMID:Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene. 1280 99

Neurocysticercosis (NCC) remains a major public health problem in developing countries as it is the most common helminthic infection of the central nervous system. Clinical manifestations are non-specific and pleomorphic. Case reports on uncommon presentations of NCC are few. We report six interesting cases of NCC with unusual clinical presentation that demonstrate this spectrum of pleomorphism. These include extrapyramidal disease (parkinsonism and focal dystonia), Kluver-Bucy syndrome, Weber's syndrome, dementia and cortical blindness. The clinical details and possible mechanisms for the uncommon presentations are also discussed. Thus, a high level of suspicion should be kept for NCC, especially in endemic zones and developing countries.
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PMID:Pleomorphism of the clinical manifestations of neurocysticercosis. 1621 95

Mohr-Tranebjaerg syndrome (MTS) is an X-linked disorder characterized by childhood-onset progressive deafness, dystonia, spasticity, mental deterioration, and blindness. It is due to mutations in the deafness/dystonia peptide (DDP1) gene. We describe a sporadic 42-year-old man with MTS presenting with postlingual deafness, adult-onset progressive dystonia with marked arm tremor, mild spasticity of the legs, and visual disturbance due to a novel mutation (g to a transition at the invariant gt of the 5' splice donor site of exon 1) in the DDP1 gene. This case, and a review of previously reported cases, highlights a variety of potential diagnostic pitfalls in this condition.
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PMID:Blepharospasm and limb dystonia caused by Mohr-Tranebjaerg syndrome with a novel splice-site mutation in the deafness/dystonia peptide gene. 1753 80

Patients harboring A467T and W748S POLG1 mutations present with a broad variety of neurological phenotypes, including cerebellar ataxia, progressive external ophthalmoplegia (PEO), myoclonus, epilepsy, and peripheral neuropathy. With exception of ataxia and myoclonus, movement disorders are not typical features of POLG1 associated disorders. We report on two affected siblings compound heterozygous for A467T and W748S mutations, one suffering from choreoathetosis and apraxia of lid opening due to focal eyelid dystonia that mimicked progression of ptosis, resulting in functional blindness. So far, focal dystonia has not been reported in POLG1 mutation carriers, and should be considered when investigating patients with PEO and ptosis. Further studies on POLG1 mutations in focal dystonia are warranted.
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PMID:Apraxia of lid opening mimicking ptosis in compound heterozygosity for A467T and W748S POLG1 mutations. 1854 43


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