The contribution of pathology to the study of storage disorders

Our purpose is to illustrate some contributions of pathology to a better knowledge of metabolic disorders affecting the brain and visceral organs. Four groups of diseases are used to that effect. A comparative study of pre- and postnatal examples of mucopolysaccharidoses I, II and III reveals for example that severe neuronal lesions are already found in fetuses and that a rough parallelism exists between the maturation of neurons and the progressive intralysosomal accumulation of undigested metabolites. The study of four patients with I-cell disease shows that the intralysosomal storage occurs nearly exclusively in fibroblasts. Since the enzyme defect has also been found in non-mesenchymal cells, other mechanisms for a proper processing of lysosomal enzymes must be available in the intact cells. Adrenoleukomyeloneuropathy is used to demonstrate that the morphological features witnessing the accumulation of the very long chain fatty acids can be different in the central and in the peripheral nervous system. Finally, juvenile dystonic lipidosis illustrate the heterogeneity of the conditions grouped under the denomination of sphingomyelinoses. These few examples confirm the role of pathology in the diagnosis of metabolic disorders and in the study of their physiopathogenesis.