Eight At One Stroke: Attention Gangliosidoses A Registry Study for Patients With Gangliosidoses

1. Aim of the Project

• The aim of the project is to collect fundamental epidemiological and clinical data, such as prevalence and incidence, but also data regarding phenotype, diagnosis and mutation spectrum.
• To understand the natural course of these diseases seems to be very important for individual advice of families and additionally for planning drug studies.
• In this study it should also be analyzed how the families and their setting have perceived the disease manifestation. Their perception will be compared to clinical findings and symptoms that were noticed by the physician. The medical history may indicate which symptoms and findings may lead to a well-directed diagnosis.
• Clinical and genetic data, that also concern aspects of social medicine, of a greater cohort will raise the awareness of pharmaceutical companies that develop new drugs and will increase the chance of patients to participate in a clinical trial.
• The project will enable validation of biomarkers that may be useful for diagnostic purposes and also for monitoring laboratory parameters during a trial.
• Patients and their families are involved in the development and procedure of the study. They become a voice and are noticed as partners in the public health service.

3. Background 3.1 Gangliosidoses Gangliosidoses represent autosomal-recessive lysosomal storage disorders, caused by a defect in the lysosomal degradation of gangliosides, resulting in accumulation of these substrates in several organs. Gangliosidoses are divided in eight different diseases according to their biochemical and genetic defect: Four disorders are assigned to GM2-Gangliosidoses, four belong to the Neuraminidase-ß-Galactosidase complex. Gangliosidoses are characterized by more or less pronounced progressive loss of mental and motor capabilities. In patients with a more attenuated phenotype the diagnosis is done often very late, as the typical clinical "classical" features are commonly lacking. Maybe adult patients were never diagnosed.

The diseases result from the accumulation of gangliosides, caused by genetic defects of enzymes or other proteins that are involved in the lysosomal degradation of these complex lipids.

3.2 Classification of Gangliosides GM1-Gangliosidosis - Sialidosis