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)

There is now a great deal of evidence to link genetic defects of pyruvate metabolism to brain disease. Experimental evidence is reviewed in Chapter 12, and clinical evidence has been reviewed above. Severe lesions of components of the pyruvate dehydrogenase complex are associated with severe generalized brain disease, and milder defects with inherited ataxias. Nearly half of one series of our ataxic patients had deficient activity of pyruvate dehydrogenase, and 40% of another series have deficient activity of the lipoamide dehydrogenase component. This last group corresponds to 60% of the patients with Friedreich's ataxia and its clinical variants at UCLA. There is an association between defective activity of lipoamide dehydrogenase and disease, and the data suggest there is a structural mutation of the gene for the enzyme. Preliminary studies suggest that obligate heterozygotes as a group have enzyme activities between those for controls and those for patients. Moreover, the obligate heterozygotes from families in which there are kinetic defects of lipoamide dehydrogenase also appear to have kinetic abnormalities of the enzyme. The ataxic patients with reduced lipoamide dehydrogenase activity currently fall into two clinical groups. One is ragged-red ataxia, and the other is a disorder that is a subgroup of the classic Friedreich's ataxia syndrome. Studies need to be undertaken on a larger group of patients, with more diverse inherited ataxias, to test the present clinical associations of the enzyme defect. A dietary treatment derived from a knowledge of the presumed defect has modified the ataxia that is associated with defects of pyruvate decarboxylase, but the diet has not yet been tested with defects of lipoamide dehydrogenase.
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PMID:Evidence for a primary defect of lipoamide dehydrogenase in Friedreich's ataxia. 10 55

A partial deficiency of pyruvate decarboxylase (PDC) was demonstrated in a child with hyperlactatemia and progressive ataxia, bulbar paresis, ophthalmoplegia, and polyneuropathy. Subacute necrotizing encephalomyelopathy (SNE) was found at necropsy. The association of SNE and PDC deficiency has been reported rarely, but a review of the diverse metabolic defects associated with SNE suggests that decreased PDC activity may be the common feature of SNE.
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PMID:Pyruvate decarboxylase deficiency in subacute necrotizing encephalomyelopathy. 724 88

Pyruvate dehydrogenase deficiency is one of the most common causes of encephalopathy associated with lactic acidosis and is known to account for congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome. Hitherto, however, peripheral neuropathy has not been regarded as a presenting symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon reflexes, and reduced motor nerve conduction velocities at 8 months of age. Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma were highly suggestive of a pyruvate dehydrogenase deficiency, and the determination of pyruvate dehydrogenase activity in circulating lymphocytes led to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband. Based on this observation, we suggest that pyruvate dehydrogenase deficiency should be considered in the diagnosis of peripheral neuropathy in infancy, especially when associated with persistent hyperpyruvicemia, normal lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and hypotonia of unknown origin.
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PMID:Leigh syndrome: pyruvate dehydrogenase defect. A case with peripheral neuropathy. 815 Oct 84