1. BioSly - Biomarker for Sly disease

BioSly - Biomarker for Sly disease

Clinical trial started on October 23, 2014

Synopsis

Mucopolysaccharidosis type VII (also known as Sly syndrome) 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.

New methods, such as mass-spectrometry, provide a good chance o characterizing specific metabolic alterations in the blood (plasma) of affected patients, and in the future will allow earlier diagnosis of the disease, with higher sensitivity and specificity.

Therefore, it is the goal of this study to identify and validate a new biochemical marker from the plasma of the affected patients, helping to benefit other patients with early diagnosis and thereby with earlier treatment. Examining saliva samples will allow us to determine whether measurement is feasible in saliva samples and will further promote early detection of Sly disease.


Background information

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.

To date, 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 under the ceiling for orphan designation, which is 5 people in 10,000.