Metachromatic leukodystrophy is an inherited disorder characterized by a deficiency of the lysosomal enzyme arylsulfatase A and the subsequent accumulation of sulfatide in neural and visceral tissues. Clinical diagnosis is usually confirmed by in vitro analysis of arylsulfatase A activity, but may be complicated in cases of arylsulfatase A pseudodeficiency and sphingolipid activator protein deficiency. Large quantities of sulfatide can be detected in the urinary sediment of affected individuals and its measurement can aid in diagnosis. A number of complex methods have been described for the measurement of urinary sulfatide excretion. We have developed a rapid, sensitive, and specific mass spectrometric method for determining urinary sulfatide concentration of metachromatic leukodystrophy patients. Sulfatides are extracted from urine and then directly analyzed using electrospray ionization-tandem mass spectrometry. A sulfatide internal standard has been employed for quantification. The assay has demonstrated significant elevations in the concentrations of several hydroxy and nonhydroxy molecular species of sulfatide in the urine of metachromatic leukodystrophy patients compared to age-matched controls. Analysis of urinary sulfatides in arylsulfatase A pseudodeficiency patients showed a mild elevation in some individuals when related to urinary phosphatidylcholine.
- Child, Preschool
- Leukodystrophy, Metachromatic
- Mass Spectrometry
Whitfield, P. D., Sharp, P. C., Johnson, D. W., Nelson, P., & Meikle, P. J. (2001). Characterization of urinary sulfatides in metachromatic leukodystrophy using electrospray ionization-tandem mass spectrometry. Molecular Genetics and Metabolism, 73(1), 30-7. https://doi.org/10.1006/mgme.2001.3165