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© 1980 American Academy of Neurology Preclinical diagnosis and carrier detection in ataxia associated with abnormalities of lipoamide dehydrogenaseAtaxia Clinic, Department of Neurology, and the bed Neurological, the Jerry Lewis Neuromuscular, and the Mental Retardation Research Centers, UCLA School of Medicine, Los Angeles, CA. 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 µM lipoamide (mean ± SEM) versus 56 ± 9 µM for controls (p < 0.001), and KmH for the patients was 421 ± 19 µM versus 147 ± 14 µM for the controls (p < 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 µM; average KmH, 378 ± 47 µM, p < 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. Address correspondence and reprint requests to Dr. Kark, Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, CA 90024. This work was supported in part by NIH grants Nos. NS-15245, HD-06576, HD-04612, and HR-865 from the USPHS; grants from the Muscular Dystrophy Association, the Imm R. Mayer Foundation, and the Easter Seal Research Foundation; donations from Mrs. Marjorie L. Johnson, the Friedreich's Ataxia Group in America, the Scott Fund, and the National Ataxia Foundation; and a postdoctoral research fellowship from the Muscular Dystrophy Association to Dr. Maria Rodriguez-Budelli. Accepted for publication August 14, 1979
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