Background: Glycosaminoglycan analysis for the diagnosis of Morquio patients has been daunting due to lack of sensitivity/specificity of the dimethylmethylene blue-based spectrophotometry methodology, routinely used by several clinical laboratories. MS methods have been devised for quantification of keratan sulfate for Morquio patients, but some used tributylamine in mobile phases, or did not use isotope-labeled internal standards. Results & methodology: An UPLC-MS/MS methodology aiming to solve these issues was devised, based on the digestion of keratan sulfate to obtain two major disaccharides. Abnormal urinary results were obtained for all Morquio A patients, while the dimethylmethylene blue-based spectrophotometry methodology showed normal results for four out of nine cases.
Conclusion: The devised method is sensitive, specific and suitable for high-risk screening and longitudinal evaluation of treated patients.
Keywords: MPS IVA; MS; Morquio A syndrome; UPLC–MS/MS; diagnosis; keratan sulfate; mucopolysaccharidosis.