[Strategies for the diagnosis of lysosomal storage diseases: symptoms, methods and samples]

Lysosomal diseases are a group of about 30 genetic defects with a total incidence of 3 to 4 cases/10,000 newborns. Their clinical appearance is very heterogeneous and comprises infantile, as well as juvenile or adult forms. Our concept for their diagnosis has now been in use for eight years and entails the following strategy: The three main symptom groups coarse facial features, visceromegaly and/or psychomotor retardation should be examined for their typical expression and for the occurrence of specific "key symptoms". Thereafter, biochemical analysis of urine for oligosaccharides, mucopolysaccharides and in some cases, of sphingolipids or direct enzyme assays in serum, peripheral leucocytes or skin fibroblasts are performed. The selection of appropriate methods is usually the domain of the biochemist and greatly depends on the available samples and the quality of clinical information. The diagnostic value and the limitations of methods and samples are discussed in detail. Finally, evidence of defects in the expression of relevant gene products, such as enzymes, activator proteins or transport proteins can be obtained and used for genetic counselling and/or for prenatal diagnosis in chorionic villi or cultured amniotic fluid cells. Our results confirm the data on the high incidence of mucopolysaccharidoses I and III A. In addition, a comparatively high number of otherwise rare diseases, such as fucosidosis or sialic acid storage disease was found. Among the group of sphingolipidoses, special attention should be paid to juvenile or adult forms.