Approximately 60 lysosomal storage diseases are known worldwide, but so far only about a dozen of these metabolic diseases have been biochemically understood and become amenable to treatment. In a collaboration project, the Steinbeis Innovation Center for Biopolymer Analysis and Biomolecular Mass Spectrometry at the University of Konstanz, and Centogene GmbH are developing and validating new molecular methods for the diagnosis of lysosomal storage diseases, and for application of these methods to clinical diagnosis. Based on mass spectrometry and fluorescence spectroscopy, the new methods form the basis for the development of rapid and highly specific enzyme test systems that can be used to reliably and unequivocally diagnose enzyme defects, including newborn diagnostics.
Lysosomes, a type of membrane vesicle, are responsible for degrading and metabolizing endogenous substances such as lipids, carbohydrates and proteins. If the body lacks activity of any of these enzymes due to a congenital defect, or if they are inactive for biochemical reasons, lysosomal storage diseases such as Gaucher’s Disease, Niemann- Pick Disease and Fabry Disease are resulting. These diseases have a broad spectrum of symptoms, including bone deformation, enlargement of heart and liver, and even stroke. The currently known incidence of lysosomal storage diseases is one in ca. 7000 births. Targeted enzyme therapies for some of these diseases have already been developed, but the key to treating storage diseases is a specific and early diagnosis, as enzyme replacement therapy (ERT) is often no longer effective in late stages of the disease. The aim of the joint project between Centogene and the Steinbeis Innovation Center is to synthesize highly specific new substrates for determining activities of lysosomal enzymes, that can be used both for diagnostics by mass spectrometry, and by routine clinical determination using fluorimetric analysis. Moreover, the project aims at developing methods for the simultaneous determination of multiple enzymes (multiplex diagnostics), and new diagnosis methods based on the direct determination of lysosomal enzymes. By developing these methods, the team of experts hopes to substantially broaden the diagnostics spectrum for lysosomal storage diseases. The molecular-specific determination will enable to analyze previously nondiagnosable storage diseases that are fatal if untreated, but have a good, curative prognosis if specifically diagnosed and treated early.