Me. Vazquezmemije et al., COMPARATIVE BIOCHEMICAL-STUDIES IN FIBROBLASTS FROM PATIENTS WITH DIFFERENT FORMS OF LEIGH-SYNDROME, Journal of inherited metabolic disease, 19(1), 1996, pp. 43-50
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.