Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots

Background: Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD), which is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). MPS VI is characterized by severe skeletal abnormalities, somatic tissue pathology and early death. Treatment possibilities include bone marrow transplantation (BMT) and enzyme replacement therapy (ERT; currently in phase III clinical trial). Early diagnosis of NIPS VI will allow treatment before the onset of irreversible pathology. Methods: Sensitive immune assays have been developed to detect 4-sulfatase protein and activity in normal control and NIPS VI blood-spots. Results: Dried blood-spots from MPS VI patients contained no detectable 4-sulfatase protein and activity, compared to 3.5-21 mug/L of 4-sulfatase protein and 291-1298 nmol/min/L of activity for normal human controls. In this evaluation study, the assay was sensitive and 100% specific, allowing reliable detection of individuals with MPS VI. Conclusions: The assays reported here have the potential to detect MPS VI patients using dried blood-spots. (C) 2004 Elsevier B.V. All rights reserved.