Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples.

摘要: BACKGROUND: Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by deficiency in arylsulfatase A activity, leading to accumulation of sulfatide substrates. Diagnostic and monitoring procedures include demonstration reduced activity peripheral blood leukocytes or detection sulfatides urine. However, the development a screening test challenging because instability enzyme dried spots (DBS), widespread occurrence pseudodeficiency alleles, lack available urine samples from newborn programs. METHODS: We measured individual profiles DBS (DUS) MLD patients with LC-MS/MS identify markers discriminatory power differentiate affected individuals controls. also developed method for converting all molecular species into single species, allowing quantification positive-ion mode upon derivatization. RESULTS: In patients, we found up 23.2-fold 5.1-fold differences total concentrations early- late-onset MLD, respectively, compared controls pseudodeficiencies. Corresponding DUS revealed 164-fold 78-fold patient The use converted simplified analysis increased sensitivity mode, providing second option analysis. CONCLUSIONS: This study suggests feasibility mass spectrometry sets stage larger-scale pilot study.