Improving arylsulfatase activity determination in dried blood spots: Screening and diagnostic approaches for Maroteaux–Lamy syndrome (MPS VI)

Update on the fluorometric measurement of enzymatic activities for Lysosomal Storage Disorder detection: The example of MPS VI.

“…The β-MU is particularly sensitive to blood component quenching, and is mainly attributed to hemoglobin. We showed in Franco et al 1 that ARSB EA values were significantly underestimated when β-MU calibration curves were prepared in matrices different from that of the sample reaction matrix. Oemardien et al 25 proved that ridding hemoglobin from DBS-derived reaction solutions increased β-MU fluorescence for several and have been somewhat overlooked by the scientific community and pharmaceutical industries.…”

“…We stand by these initiatives, and have a strong motivation driving our research in regards to LSD and the expansion of NBS programs. We figured that the technical approach to the ARSB EA measurement we put forward in Franco et al 1 could be adapted both for MPS VI diagnostics as well as for a NBS approach. At either end of the spectra, the number of patient samples analyzed at a time sets the bar in terms of costs, practicality, diagnostic specificity and sensitivity requirements.…”

“…In our previous research article Improving arylsulfatase activity determination in dried blood spots: Screening and diagnostic approaches for Maroteaux-Lamy syndrome (MPS VI) 1 , we adapted the protocol of Civallero et al 13 to demonstrate the significant effect that certain DBSderived compounds had on the β-MU fluorescence when measuring ARSB EA. We therefore provide strategies to overcome these problems both for confirmatory diagnostic tests, as well as for implementing this fluorometric method for MPS VI screening, such as a newborn screening (NBS) program.…”

“…We prefer DBS as the sample of choice for our protocol, since it is readily available for NBS programs and the Guthrie cards have the advantage of easy and inexpensive transport. Similar to other protocols, the determination of ARSB EA in DBS described in Franco et al 1 was adapted to use a single dried blood-impregnated filter paper disc measuring 3 mm in diameter for each sample.…”

“…The present work is based on our research article authored by Franco et al 1 where we studied the effect of blood-derived hemoglobin, and other blood components, on the fluorescence of 4-Methylumbelliferone when measuring ARSB enzyme activity from dried blood spot (DBS) samples.…”