Laboratory diagnosis of Fabry disease:: historical perspectives and recent breakthroughs

Due to its high sensitivity and specificity, determination of the alpha-galactosidase A activity in leukocytes is the gold standard to confirm the diagnosis of Fabry disease in hemizygous moles. In contrast, heterozygous females cannot be dependably diagnosed by this method and genotyping should always be carried out. Two recent breakthroughs hove contributed to the rise of screening programs for Fabry disease: first, the use of filter papers to collect blood or urine spots from individuals in at-risk populations for Fabry disease, second, the development of mass spectrometry. Substrate accumulation and enzyme activity con be measured on urine and blood samples, respectively. Mass spectrometry allows the qualitative and quantitative determination of the accumulation of the undegraded substrate (globotriaosylceromide) in urine, but also the measurement of enzyme activities in blood samples for the simultaneous diagnosis of several inborn errors of metabolism, among which lysosomal storage diseases and in particular Fabry disease.