Biomarker for Sly Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

Brief Summary

Detailed Description

Mucopolysaccharidosis type VII (also known as Sly syndrome or Sly disease) is an inherited disease caused by a lack of the enzyme beta-glucuronidase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). If the enzyme is not present, GAGs cannot be broken down and they build up in the cells and damage them. This causes a wide range of problems such as short stature, skeletal abnormalities, joint stiffness, enlarged spleen and liver, lung infections, heart problems and hernias. Patients usually die within the first year of life, although some survive into their teenage years. Mucopolysaccharidosis type VII is a life-threatening disease with many patients dying in early childhood. It also debilitating due to the physical and skeletal abnormalities that occur. Sly syndrome is characterized by coarse facial features, hepatosplenomegaly, protruding sternum and dystosis multiplex. Dystosis multiplex refers to a constellation of skeletal abnormalities and is characterized by an enlarged skull, thickened calvarium, premature closure of lamboid and sagittal sutures, shallow orbits, enlarged J-shaped sella and abnormal spacing of the teeth with dentigerous cysts. There is anterior hypoplasia of the lumbar vertebrae, the long bone diaphyses are enlarged and an irregular appearance of the metaphyses. The epiphyseal centers not well developed, the pelvis is poorly formed with small femoral heads and coxa valga. The clavicles are short, thick and irregular and the ribs are oar shaped. Phalanges are shortened and trapezoidal in shape. At the time of designation, mucopolysaccharidosis type VII affected approximately 0.001 in 10,000 people in the European Union (EU)\*. This is equivalent to a total of around 50 people, and is below the ceiling for orphan designation, which is 5 people in 10,000. New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to identify and validate a new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

Primary Outcomes

Secondary Outcomes

• Testing for clinical robustness, specificity and long-term stability of the biomarker(36 months)