Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.