Preclinical diagnosis and carrier detection in ataxia associated with abnormalities of lipoamide dehydrogenase

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.