Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

Frank Roels, P. Verloo, Francois Eyskens, François Baudouin, Sara Seneca, Boél De Paepe, Jean-Jacques Martin, V.a. Meersschaut, M. Praet, E. Scalais, M Espeel, Joél Smet, G. Van Goethem, Rudy Van Coster

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16 Citations (Scopus)


In muscle cytochrome oxidase (COX) negative fibers (mitochondrial mosaics) have
often been visualized.
COX activity staining of liver for light and electron microscopy, muscle stains, blue
native gel electrophoresis and activity assays of respiratory chain proteins, their
immunolocalisation, mitochondrial and nuclear DNA analysis.
Three unrelated infants showed a mitochondrial mosaic in the liver after staining for
COX activity, i.e. hepatocytes with strongly reactive mitochondria were found
adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was
most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were
absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in
muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue,
but not of muscle, demonstrated a decreased activity of complex IV; in both muscle
and liver subcomplexes of complex V were seen. Immunocytochemistry of complex
IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain
revealed severe white matter cavitation in the Pearson case, but only slight cortical
atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in
leucocytes showed a common deletion in 50 % of the mtDNA molecules of the
Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome,
mtDNA was depleted for 60 % in muscle. In the 3rd patient muscular and hepatic
mtDNA was depleted for more than 70 %. Mutations in the nuclear encoded gene of
POLG were subsequently found in both the 2nd and 3rd patients.
Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the
pathogenesis; it indicates whether mtDNA should be assayed. Each time a
mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy
should be recommended. Mosaics are probably more frequent than observed until
now. A novel pathogenic mutation in POLG is reported.
Tentative explanations for the mitochondrial mosaics are, in one patient, unequal
partition of mutated mitochondria during mitoses, and in two others, an interaction
between products of several genes required for mtDNA maintenance
Original languageEnglish
Article number4
Number of pages12
JournalBMC Clin Pathol
Issue numberJune
Publication statusPublished - 5 Jun 2009


  • mitochondrial disorders
  • cytochrome oxidase (COX) negative fibers
  • Alpers-Huttenlocher patient
  • Pearson syndrome patient
  • mitochondrial depletion
  • mtDNA
  • common deletion


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