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)

Mitochondrial disorder is an inborn error of metabolism affecting the cellular respiratory chain. Defective energy production leads to a wide variety of clinical manifestations (ataxia, epilepsy, dementia, myopathy, polyneuropathy, retinal pigment anomalies, and cardiomyopathy with conduction anomalies). Hearing loss is a regular feature and is often the first clinical symptom. Audiologic data from 26 members of a family in three generations is presented. One of these patients was examined for the biochemical error. Respiratory study of muscle biopsy revealed a mild defect in the NADH-ubiquinone oxidoreductase step of the oxidative phosphorylation (complex I). The content of cytochrome aa3 (complex IV) was also reduced. Adult onset sensorineural hearing loss starting in the high frequency region progresses with a fairly constant speed in this family. A cochlear type of hearing loss is found in the less pronounced cases. Advanced cases present features of retrocochlear affection with decreasing speech recognition, elevated acoustic reflex thresholds, and increased ABR latency with derangement of potentials. Caloric sensitivity was unaffected.
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PMID:Audiologic findings in a family with mitochondrial disorder. 180 40

The organophosphorus compound, triphenyl phosphite (TPP), caused ataxia in chickens 8-14 days after single po or iv administration. The po and iv ED50 values were 1414 and 35.4 mg/kg, respectively. Chickens which developed ataxia lost 14.4 +/- 2.5% (mean +/- SEM, n = 14) of their initial weight at 28 days and the paralyzed birds showed a severe reduction of 29.3 +/- 2.9% (n = 13) of their initial weight at death or at 28 days after dosing. For the first 4-hr interval after iv injection of 50 mg/kg, the elimination of TPP from plasma consisted of at least two exponential phases; the half-lives of the first and second phases were approximately 30 and 60 min, respectively. When the birds received 100 mg/kg (iv) fatty tissue showed the highest TPP concentration, e.g., 215 micrograms/g fresh wt at 6 hr postdosing. The half-life was approximately 24 hr. Among neural tissues, the sciatic nerve had the highest concentration, followed by the spinal cord, the cerebellum, and the cerebrum. The red muscles, such as adductor magnus, contained about 4-30 times as much TPP as did the white muscles, such as biceps brachii, 6 hr after treatment. Time course effects of TPP treatment on mitochondrial enzymes in leg skeletal muscles were examined by treating hens with 50 mg/kg (iv) and euthanizing the birds at 6 hr to 8 days postdosing. The creatine kinase (CK) activities of the adductor and the soleus were significantly decreased at 2 (48 hr), 4, and 8 days, and at 4 and 8 days postdosing, respectively. Adductor magnus and soleus succinate dehydrogenase (SDH) activities were decreased markedly at 24 and 48 hr, and at 2 (48 hr), 4, and 8 days, respectively. Cytochrome oxidase (COD) activity in adductor magnus and soleus did not decrease during the time course. Biceps femoris CK, SDH, and COD activities were not affected by TPP treatment at this dosage. These results suggest that TPP administration affects the mitochondrial metabolism in skeletal muscle, especially red muscle of chickens.
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PMID:Delayed neurotoxicity of triphenyl phosphite in hens: pharmacokinetic and biochemical studies. 278 68

Identical twins developed myoclonic epilepsy in their teens. One twin remained mildly affected but the other went on to develop sensorineural deafness and ataxia with lactic acidosis and ragged red fibres leading to a diagnosis of mitochondrial encephalopathy. Multiple stroke-like episodes with hemiparesis followed, indicating progression from a MERRF to a MELAS phenotype. Biochemical studies revealed a severe deficiency of mitochondrial NADH-ubiquinone reductase and a moderate deficiency of cytochrome aa3. Western immunoblotting experiments using polyclonal antibodies raised against human placental cytochrome oxidase identified a similar profile of bands to those seen in controls, supporting the view that cytochrome aa3 deficiency in this case may be a secondary consequence of a failure of assembly related to a severe proximal respiratory chain defect.
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PMID:Progression from MERRF to MELAS phenotype in a patient with combined respiratory complex I and IV deficiencies. 285 17

The son of third cousins was normal until age 2 when he had difficulty walking. At age 8 there was limb weakness, ataxia, loss of tendon reflexes, dislalia, and he was mildly retarded. During fasting, urinary organic acid excretion was abnormally high. Cytochrome c oxidase activity in muscle was 7% of the normal mean. The enzyme in platelets was 16% of controls with a decreased cytochrome aa3 peak. These data suggest an autosomal recessive transmission of this variant of cytochrome c oxidase deficiency.
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PMID:Childhood encephalomyopathy with cytochrome c oxidase deficiency, ataxia, muscle wasting, and mental impairment. 301 3

The paroxysmal dyskinesias are a group of neurological disorders described by intermittent attacks of involuntary abnormal movements superimposed on a relatively normal baseline. The neuroanatomical substrates for these attacks are not fully understood, though available evidence from studies of affected people and animal models points to dysfunction in the basal ganglia or cerebellum. In the current studies, the anatomical basis for paroxysmal dyskinesias in lethargic mice was determined via histochemical methods sensitive to changes in regional brain activity followed by surgical elimination of the suspected source. Cytochrome oxidase histochemistry revealed increased activity in the red nucleus. Surgical removal of the cerebellum worsened ataxia but eliminated paroxysmal dyskinesias. These studies support the hypothesis that abnormal cerebellar output contributes to paroxysmal dyskinesias.
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PMID:Neuroanatomical substrates for paroxysmal dyskinesia in lethargic mice. 1756 8