Electron microscopy continues to play an important role in the diagnosis of paediatric disorders especially when integrated with molecular biology, biochemistry, and other relevant investigations. EM also provides valuable information to research groups to gain an insight into cellular morphology, function, and imbalances in disease processes. Ultrastructural information is particularly valuable in the following fields:
A major area of work in paediatrics involves the interpretation of renal biopsies, by light microscopy, immunocytochemistry, and EM. Many conditions relate to glomerular disease, but EM is also valuable in the study of tubular, interstitial and vascular lesions. Immune complexes in systemic lupus erythematosus can be accurately detected ultrastructurally in the glomerulus and this can help to confirm the histological pattern or class of the disorder. Of particular importance is the assessment of the glomerular basement in thin basement membrane disease and Alport’s disease a hereditary disorder resulting in thickening and splitting of the GBM.
In paediatrics, skeletal muscle and cardiac muscle biopsies are examined for mitochondrial disorders, nemaline rod myopathy and other structural abnormalities and inclusions.
Peripheral nerves can provide information in some rare storage disorders including metachromatic leukodystrophy and infantile neuroaxonal dystrophy which results in swollen axons with tubulovesicular inclusions.
LSD are a group of about 50 rare, inherited diseases characterized by an abnormal build-up of toxic materials in the body’s cells as a result of enzyme deficiencies. Storage is present in a variety of organs and cell types resulting in the formation of large intracellular lysosomal inclusions. Diagnosis is reinforced by biochemistry and molecular biology, but EM can help to identify some variant forms of the disease and save time to target the appropriate gene. Morphological diagnosis is made using a variety of tissues including blood and skin biopsies. Batten’s disease is a progressive neurological disorder with many subtypes. EM can help to identify the unusual profiles seen in some of these disorders which may be missed by other investigations.
Infants with severe diarrhoea may exhibit abnormalities of their intestinal microvilli. In congenital microvillus inclusion disease this brush border may be irregular and rare involutions of microvilli may be identified in the apical cytoplasm of enterocytes in the small and large intestine. Other conditions where EM may be of benefit include the pseudo- obstruction motility disorders caused by nerve or muscle problems.
Some centres prefer to use punch biopsy of skin for storage disorders as there is a greater variety of cell types to examine. Batten’s disease, neuroaxonal dystrophy and Lafora disease are examples. Ultrastructural analysis is of value in confirming the diagnosis of a group of rare, inherited, blistering skin disorders, epidermolysis bullosa. Any trauma or friction can cause blistering of the skin. EM is used to identify where the level of splitting occurs, supporting diagnosis of the disorder type.