Abstract
Mitochondrial dysfunction of the energy generating system was suggested in two infants
with progressive infantile poliodystrophy characterised by hypotonia, refractory epilepsy,
visual impairment, psychomotor retardation, profound brain atrophy, hepatopathy, and
increased levels of lactate in blood and cerebrospinal fluid. Histochemical and electron
microscopic analyses of liver biopsies revealed cytochrome c oxidase deficiency, microvesicular steatosis, and enormous multiplication of mitochondria
of various sizes. In the first patient, the quantitative Southern blot analyses in
tissues obtained at autopsy demonstrated reduced content of mtDNA in the liver, brain,
and fibroblasts (11 %, 15 %, and 25 % of the mean values in controls) while a normal
content of mtDNA was found in muscle and heart. In the second patient, a reduced content
of mtDNA was found in the muscle, liver, and brain (15 %, 10 %, and 30 %, respectively,
of the mean values in controls). Biochemical studies in the first patient revealed
decreased activities of all respiratory chain complexes except complex II in isolated
liver mitochondria and decreased amounts of respiratory chain complexes I, III, IV
and ATP synthase in liver and frontal cortex, but not in muscle, heart, and fibroblasts.
In conclusions, mtDNA depletion associated with Alpers syndrome may be tissue specific.
Key words
MtDNA depletion - respiratory chain complexes - Alpers syndrome
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Prof. M. D., PhD Jiri Zeman
Department of Paediatrics
Faculty of Medicine
Charles University
Ke Karlovu 2
12808 Prague 2
Czech Republic
Email: jzem@lf1.cuni.cz
