Characterization of urinary sulfatides in metachromatic leukodystrophy using electrospray ionization-tandem mass spectrometry

Metachromatic leukodystrophy is an inherited disorder characterized by a de ficiency of the lysosomal enzyme arylsulfatase A and the subsequent accumul ation of sulfatide in neural and visceral tissues. Clinical diagnosis is us ually confirmed by in vitro analysis of arylsulfatase A activity, but may b e complicated in cases of arylsulfatase A pseudodeficiency and sphingolipid activator protein deficiency. Large quantities of sulfatide can be detecte d in the urinary sediment of affected individuals and its measurement can a id in diagnosis. A number of complex methods have been described for the me asurement of urinary sulfatide excretion. We have developed a rapid, sensit ive, and specific mass spectrometric method for determining urinary sulfati de concentration of metachromatic leukodystrophy patients. Sulfatides are e xtracted from urine and then directly analyzed using electrospray ionizatio n-tandem mass spectrometry. A sulfatide internal standard has been employed for quantification. The assay has demonstrated significant elevations in t he concentrations of several hydroxy and nonhydroxy molecular species of su lfatide in the urine of metachromatic leukodystrophy patients compared to a ge-matched controls, Analysis of urinary sulfatides in arylsulfatase A pseu dodeficiency patients showed a mild elevation in some individuals when rela ted to urinary phosphatidylcholine. (C) 2001 Academic Press.