Methodology in evaluating pyruvate oxidation.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
M Rodriguez-Budelli
Publications and source records attributed to M Rodriguez-Budelli.
Pyruvate dehydrogenase deficiency in spinocerebellar degenerations.
To study the incidence of abnormalities of the pyruvate (PDH) or ketoglutarate (KGDH) dehydrogenase complexes in patients with spinocerebellar degenerations, we measured the activities of PDH and KGDH in platelet-enriched preparations from the blood of 14 patients. Low PDH was found in 6 of the 14 patients; low KGDH was found in 2 of the 6. PDH-normal and PDH-abnormal patients could not be distinguished by clinical criteria. These results extend previous studies, which suggested abnormalities of pyruvate oxidation in patients with hereditary ataxias. The data imply that deficient activity of the PDH complex may be associated with spinocerebellar degenerations, and that the clinical phenotypes of the inherited ataxias can be associated with several genotypes.
Adolescent↗
Pyruvate dehydrogenase deficiency in 35 patients.
Explore the source record for details and available documents.
Acidosis↗
Kinetic evidence for a structural abnormality of lipoamide dehydrogenase in two patients with Friedreich ataxia.
Two unrelated patients with Friedreich ataxia were deficient in the activity of the enzyme lipoamide dehydrogenase (LAD). The enzymes from the patients' platelets differed significantly from controls in activity, in KM for lipoamide, and in KM for NADH. The data are consistent with a structural mutation of the gene coding for LAD.
Adolescent↗
Evidence for a primary defect of lipoamide dehydrogenase in Friedreich's ataxia.
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.
Ataxia↗