Mass spectrometry and two-dimensional electrophoresis in prenatal diagnosis of mucopolysaccharidosis type VI

Abstract

Abstract Background Mucopolysaccharidosis VI (MPS VI) or Maroteaux–Lamy syndrome is an autosomal recessive lysosomal storage disorder. Clinical manifestations are related to progressive accumulation of dermatan sulfate (DS). Two-dimensional electrophoresis has traditionally been used for the diagnosis of MPS disorders. The method is only qualitative and is time consuming. For prenatal diagnosis of MPS, 6–8 ml of amniotic fluid is required and 5 working days to complete. It needs personal experience to do the test and to interpret the results. Mass spectrometry (MS) is now available as a quantitative method and for prenatal diagnosis of MPS it needs less amniotic fluid and takes only 2 working days. It is more accurate, less person dependent, but it costs more. Our aim was to introduce quantitative determination of dermatan sulfate using mass spectrometry in the prenatal diagnosis of MPS VI in Egypt and to compare this technique to the classical qualitative diagnosis using two-dimensional electrophoresis (2-DEP) of the glycosaminoglycans (GAGs) in amniotic fluid. Thirty pregnant females each with single fetus were subjected to amniocentesis at 16 weeks gestation. Ten with a previously affected MPS VI infant and twenty served as controls. Prenatal diagnosis (PD) was done by both MS and 2-DEP. Results MS verified 2-DEP results which showed 5 affected and 5 non-affected fetuses with MPS VI. Conclusion Two-dimensional electrophoresis of the GAGs in amniotic fluid is a good qualitative method and MS was an accurate quantitative method for prenatal diagnosis of MPS type VI. Quantitative determination of GAGs in AF by mass spectrometry is quicker. Where prenatal diagnosis is recommended for at risk pregnancies, mass spectrometry could be used more in the future as it gives rapid and accurate results.