Abstract
In an attempt to identify a possible defect of mitochondrial metabolism in Rett syndrome we studied 9 girls with typical Rett syndrome using a clinical protocol designed to identify disorders of oxidative metabolism.
One girl, (RO) had marked lactic acidemia. Biochemical studies on samples from these
patients included leukocyte pyruvate carboxylase assay, serum biotinidase and skin
fibroblast pyruvate production, pyruvate dehydrogenase, citrate synthetase and 2-oxoglutarate
dehydrogenase assay. Muscle electron transport activities were studied on samples
from 4 typical Rett patients including RO. Mitochondrial DNA (mtDNA) mutational analysis for the np3243
MELAS mutation, the np8993 NARP mutation, the np8344 MERFF mutation and the 4977 kb
common deletion found in Kearns-Sayre syndrome and aged tissues were tested for in 1 of the muscle samples and 2 blood samples
from typical Rett patients. Western blotting of electron transport complex III was performed on mitochondrial
samples obtained from autopsy brain tissue in 2 Rett patients and compared to pediatric control brain samples.
No abnormalities were found in blood biotinidase or pyruvate carboxylase. Western
blotting of 2 Rett brain mitochondrial samples for complex III appear normal. Pyruvate consumption in
medium from 8 Rett fibroblast lines grown with and without dichloroacetate (DCA) showed a normal fall
in pyruvate suggesting normal pyruvate dehydrogenase activity in these cells, however
the fibroblasts from patient RO had a high pyruvate production in culture. Pyruvate
dehydrogenase, 2-oxo-glutarate dehydrogenase and citrate synthetase activities in
8 Rett fibroblast lines were normal. Muscle mitochondrial activities in 4 Rett patients were normal for citrate synthetase and electron transport complexes I, II/III,
III and IV (cytochrome oxidase), however, muscle cytochrome oxidase activity fell
on repetitive assay in one patient (RO) raising a question about excessive lability
of the complex in this patient to repeated freeze thawing. Muscle histochemical staining
for cytochrome oxidase in patient RO was normal. All mtDNA studies were negative.
Key words
Rett syndrome - Pyruvate dehydrogenase - 2-oxo-glutarate dehydrogenase - Electron transport
complexes - mtDNA
