COMPARATIVE BIOCHEMICAL-STUDIES IN FIBROBLASTS FROM PATIENTS WITH DIFFERENT FORMS OF LEIGH-SYNDROME

We have compared respiratory chain enzyme activities, ATP synthesis, a nd ATP hydrolysis in cultured fibroblast mitochondria from patients wi th Leigh syndrome (LS) due to: (i) cytochrome oxidase (COX) deficiency (#6); (ii) pyruvate dehydrogenase complex (PDHC) deficiency (#4); and (iii) maternally inherited LS (MILS) with the T8993G mutation in the ATPase 6 gene of mtDNA (#5). Enzyme activities were normal in patients with MILS and variably decreased in those with COX and PDHC deficienc y. ATP hydrolysis was normal or mildly decreased in all three groups. In contrast, ATP synthesis was decreased in all patients but more mark edly in those with MILS, and especially with pyruvate/malate as substr ate. These studies show that impaired ATP production is the common fea ture of all three forms of LS, but it is both more severe and more spe cific in MILS, consistent with the genetic defect.