Lysosomal Storage Diseases (LSDs) are a group of largely inherited metabolic disorders triggered by a defi ciency in lysosomal enzymes. Metabolism is impaired as a result, causing severe symptoms such as organ enlargement and cardiac muscle atrophy, which if left untreated can often be terminal, including children. Of the 60 or so LSDs that are currently known, a few can already be treated using the enzyme replacement therapy, which has high success rates where diagnosis is confi rmed. However, since fast and accurate diagnosis has so far been a major problem, affected individuals often die before treatment is possible.
The Steinbeis Transfer Center for Biopolymer Analysis, Protein Chemistry and Proteomics at the University of Constance has developed two biochemical methods for diagnosing LSDs: fluorescence spectroscopy and mass spectroscopy. These methods were validated for clinical diagnosis in conjunction with Genzyme CEE GmbH in Constance and the Biomass Spectrometry Laboratory at the University of Timisoara in Romania. A fast and reliable method of diagnosis is the dried blood spot (DBS) method, which involves determining the quantity of reaction product and thus the activity of LSD enzymes in the blood. This is particularly valuable for central and eastern European countries, where until now there have been no efficient diagnosis methods available.
The first stage of the transfer project, which was awarded the Lohn Award, involved refining the two biochemical methods and then improving diagnosis by HPLC tandem mass spectrometry so that it could be used to simultaneously diagnose multiple LSDs. The second step was to establish mass spectrometric diagnosis in the laboratories in Constance and Timisoara and to validate it using samples from clinics and from unaffected individuals.
The methods developed for the highly specific diagnosis of LSDs can be used internationally and in large-scale screening, as well as to follow up treatment. The goal of the project partners is to develop further methods on this basis to identify storage diseases that so far have proved impossible to diagnose.
Prof. Dr. Dr. h.c. Michael Przybylski
Constance Steinbeis Transfer Center for Biopolymer Analysis, Protein Chemistry and Proteomics at the University of Constance, Constance