Rare Diseases Symptoms Automatic Extraction

Morphological correlates of mitochondrial dysfunction in children.

[pyruvate dehydrogenase deficiency]

Morphological studies have traditionally played a major role in the study of adults with suspected mitochondrial diseases. Here we review their role in the investigation of paediatric patients. The morphological changes may be macroscopic, such as developmental abnormalities of the brain in pyruvate dehydrogenase deficiency, including ectopic inferior olives and the absence of corpus callosum and pyramids. Other changes are histological, such as rarefaction of the neuropil and endothelial prominence in Leigh syndrome, and spongiosis with neuronal loss and gliosis in Alpers disease. The ragged-red fibres typical of mitochondrial disease in adults are only rarely seen in skeletal muscle biopsies from children. On the other hand, dramatic ultrastructural changes involving the mitochondria may be seen in many organs, including the liver, heart and intestine. In Alpers and lethal infantile mitochondrial diseases, the hepatocytes show marked accumulation of small droplets of lipid alternating with densely packed mitochondria with pale matrix and loss of granules. These changes are associated with a marked decrease in respiratory chain enzyme activity in the liver, often without similar decrease in the skeletal muscle or fibroblasts. Enlarged mitochondria with concentric cristae are prominent in the cardiac myocytes in Barth syndrome. For the assessment of children with a suspected disorder of mitochondrial dysfunction, detailed morphological studies of the brain (at autopsy) and of biopsies (especially of the liver), including ultrastructural assessment of the mitochondria, can be a very useful preliminary investigation. The findings should then be correlated with the clinical features and used as a guide for further biochemical and molecular studies, preferably on multiple tissues.

Diseases presenting "skeletal muscle biopsies" symptom

  • inclusion body myositis
  • pyruvate dehydrogenase deficiency

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