title: Preclinical diagnosis and carrier detection in ataxia associated with abnormalities of lipoamide dehydrogenase.
abstract: To see whether kinetic assays of lipoamide dehydrogenase could be used for carrier detection or preclinical diagnosis, Michaelis-Menten constants (KmL and KmH) for the enzyme were determined in platelets from families with a form of recessive Friedreich ataxia and low activities of the enzyme. The KmL of patients' enzyme was 132 +/- 5 microM lipoamide (mean +/- SEM) versus 56 +/- 9 microM for controls (p less than 0.001), and KmH for the patients was 421 +/- 19 microM versus 147 +/- 14 microM for the controls (p less than 0.001). The activity and Km values of one patient's enzyme were abnormal 1 year before neurologic signs appeared. The Km values for the enzymes of the six parents were also elevated (average KmL, 105 +/- 10 microM; average KmH, 378 +/- 47 microM, p less than 0.02). The maximal activities of the parents' enzymes, relative to a mitochondrial marker, were intermediate between the mean maximal control activity and the mean activity for the affected offspring. The data suggest that the abnormalities of lipoamide dehydrogenase are inherited in a recessive pattern in these families.
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000201:enzymology; D002648:Child; D008058:Dihydrolipoamide Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005621:Friedreich Ataxia / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006801:Humans; D007700:Kinetics; D008297:Male
chemical_list: D008058:Dihydrolipoamide Dehydrogenase