Reduced enzyme activities in inherited ataxia

Abstract

Our group and colleagues have reported partial diminution in activities of the enzyme lipoamide dehydrogenase (LAD) in peripheral tissues of some patients with recessively inherited ataxia [ l , 31. This result extended findings of low activities of the pyruvate and the a-ketoglutarate dehydrogenase complexes (PDH and KGDH) [l] and is a possible explanation for the decreased oxidation of [2-*4C]pyruvate to 14C02 in tissues of some of the same patients. Others have not been able to find these changes in their patients [2, 41, though a recent report can be interpreted as confirming our findings with respect to P D H [5]. We have therefore undertaken a "blind" study with samples from two previous patients. Technical personnel were different from those involved in prior work.The patients were brothers: [3] except that the p H was 7.3, and in the forward direction with 250 p M nicotinamide-adenine dinucleotide at p H 8.0. The changes from prior conditions were to ensure optimal circumstances for the assays. Heat inactivation was expressed as the time taken to decrease the activity to half the initial value (t5& Cytochrome c oxidase and protein were assayed as before [3], each sample in duplicate to quadruplicate. The results are given in the Table. We have previously reported that patients could be distinguished from controls by these methods on the basis of average values from assays on three to six separate platelet samples. We believe multiple samples need to be assayed despite the lack of overlap in some of the simultaneous assays indicated in the Table. These findings confirm previous reports of abnormalities of LAD and P D H in the patients [l,

Disorders of the pyruvate dehydrogenase complex

“…Deficiencies of PDC and a-ketoglutarate dehydrogenase have been found in various tissues by some workers Maruyama and Yamaguchi, 1984) while others have found normal activity (Evans, 1983). Methodological problems may have contributed to the confusion and in some cases methodological errors have led to subsequent retractions (Kark et al, 1980(Kark et al, , 1981. Deficiencies of PDC have also been described in Huntington's disease (Sorbi et al, 1982;Butterworth et al, 1981), Alzheimer's disease (Sorbi et al, 1982) and Reye's syndrome .…”