Biomarker for Maroteaux-Lamy Disease (BioMaroteaux)

Development of a new MS-based biomarker for the early and sensitive diagnosis of Maroteaux-Lamy disease from blood

Maroteaux-Lamy disease (MPS VI) is a lysosomal storage disease inherited in an autosomal recessive pattern. The responsible mutations lie in ARSB (5q11-q13), the gene that encodes the enzyme arylsulfatase B. The phenotype results from defective dermatan sulfate break-down with lysosomal accumulation. This accumulation of glycosaminoglycans is responsible for the widespread signs and symptoms found in this disease. Bone destruction in shoulders, hips and skull is often seen by the second decade of life and may become evident later in the knees and spine. Early growth may be normal but eventually slows resulting in short stature. Dysplasia of bones comprising these joints leads to stiffness and restricted movement. The face is dysmorphic with coarse features. Bone dysplasia and facial dysmorphism may be seen at birth. Myelopathy and even tetraplegia can result from vertebral compression. Intelligence is often normal although more severely affected individuals may have some cognitive defects due to impaired vision and hearing. Hepatosplenomegaly is common and compromised respiratory function can result in reduced physical stamina. The tongue is usually enlarged. Accumulation of dermatan sulfate in heart valves may produce insufficiency or restriction of outflow. A diagnosis of Maroteaux-Lamy disease can be confirmed by screening for the common genetic mutations or measuring the level of the arylsulfatase B enzyme activity in a blood sample -- a test that has 100 percent accuracy. Once Maroteaux-Lamy disease is diagnosed, testing of all family members and consultation with a professional geneticist is recommended. Carriers are most reliably identified via genetic mutation analysis. New methods, like mass-spectrometry give a good chance to characterize in the blood (plasma) of affected patents specific metabolic alterations that allow to diagnose in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to develop new biochemical markers from the plasma of the affected patients helping to benefit the patient by an early diagnose and thereby with an earlier treatment.