Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 21-year-old woman, who had no particular familial history, was admitted to our hospital because of hand tremor and gait disturbance. On neurological examination, she showed muscle weakness in the proximal extremities. There was an ataxia on heel-to-shin testing. Action and postural myoclonus involving the extremities were also noted. In addition, with dorsiflexion of the hands, asterixis-like movement was manifested. Pyruvate was 1.0 mg/dl and lactate was 24.1 mg/dl in cerebrospinal fluid. Brain CT scan revealed mild cerebellar atrophy. EEG showed synchronous diffuse slow wave. Median nerve SEPs showed a large N20-P25 component (20 microV). Median nerve C-reflex was not evoked. With dorsiflexion of the hands, the asterixis-like movement was induced with brief cessation of surface EMG activity in the forearm muscles, as shown by the accelerometer trace. Biopsy specimens of the biceps brachii muscle revealed numerous ragged-red fibers. By PCR-RFLP method with use of a mismatched primer, we analyzed mitochondrial DNA extracted from peripheral leukocytes. The A to G mutation at nucleotide position 8,344 in a tRNA(Lys) gene of a mitochondrial genome was detected. In this patient, clonazepam was effective on the asterixis-like movements. From existence of positive myoclonus, giant SEPs and efficacy of clonazepam, we considered this movement to be negative myoclonus. Our study indicated the possibility that such an involuntary movement could be induced by certain posture in patients with MERRF.
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PMID:[Myoclonus epilepsy associated with ragged-red fibers--report of a patient with negative myoclonus]. 149 Mar 14

We report a 23-year-old woman who slowly developed progressive tremulous myoclonus and rare convulsive seizures beginning at the age of 9 and 11 years, respectively. She also showed a mild degree of ataxia and cognitive dysfunction. Convulsive seizures were well suppressed by valproic acid since the age of 17 years, but tremulous myoclonus gradually progressed and became rather intractable in spite of treatment by clonazepam and piracetam. Her cognitive dysfunction was mild (total IQ score in Wechsler Adult Intelligence Scale Revised being 85 points). In addition, she had a fear of walking which disabled her in the daily life although she could actually walk without assistance. The brain MRI showed a mild cerebellar atrophy, and FDG-PET showed a mild hypometabolism in the cerebellar hemispheres. Somatosensory evoked potentials (SEPs) showed enlarged P25 and N33 amplitudes (giant SEPs). A Cystatin B gene analysis exhibited a homozygous expansion of the dodecamer repeat, and thus we made a diagnosis of Unverricht-Lundborg disease (ULD). We also did gene analysis and SEP study to her parents after written informed consents were obtained. They had heterozygous expansion of the dodecamer repeat. The mother also showed enlarged P25 and N33 amplitudes, whereas the father showed normal amplitudes. It is known that degree of clinical symptoms varies among patients with ULD diagnosed by gene analysis. Gene analysis was helpful for a diagnosis of ULD in this patient because the ataxia and cognitive dysfunction were much milder than those commonly seen in patients with ULD.
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PMID:[Unverricht-Lundborg disease manifesting tremulous myoclonus with rare convulsive seizures: a case report]. 1922 96

HTRA2, a serine protease in the intermembrane space, has important functions in mitochondrial stress signaling while its abnormal activity may contribute to the development of Parkinson's disease. Mice with a missense or null mutation of Htra2 fail to thrive, suffer striatal neuronal loss, and a parkinsonian phenotype that leads to death at 30-40 days of age. While informative, these mouse models cannot separate neural contributions from systemic effects due to the complex phenotypes of HTRA2 deficiency. Hence, we developed mice carrying a Htra2-floxed allele to query the consequences of tissue-specific HTRA2 deficiency. We found that mice with neural-specific deletion of Htra2 exhibited atrophy of the thymus and spleen, cessation to gain weight past postnatal (P) day 18, neurological symptoms including ataxia and complete penetrance of premature death by P40. Histologically, increased apoptosis was detected in the cerebellum, and to a lesser degree in the striatum and the entorhinal cortex, from P25. Even earlier at P20, mitochondria in the cerebella already exhibited abnormal morphology, including swelling, vesiculation, and fragmentation of the cristae. Furthermore, the onset of these structural anomalies was accompanied by defective processing of OPA1, a key molecule for mitochondrial fusion and cristae remodeling, leading to depletion of the L-isoform. Together, these findings suggest that HTRA2 is essential for maintenance of the mitochondrial integrity in neurons. Without functional HTRA2, a lifespan as short as 40 days accumulates a large quantity of dysfunctional mitochondria that contributes to the demise of mutant mice.
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PMID:Neural-specific deletion of Htra2 causes cerebellar neurodegeneration and defective processing of mitochondrial OPA1. 2553 4