Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births. This study proposes Lysotracker a commercially available fluorescent probe to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. This marker was validated in a mouse model of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of NPC patients. Pediatric NPC subjects had elevated acidic compartment volume that correlated with age-adjusted clinical severity and was reduced in response to therapy with miglustat, a drug that has been shown to reduce NPC1-associated neuropathology. Measurement of relative acidic compartment volume was found to be useful for monitoring therapeutic responses of an NPC2 patient after bone marrow transplantation. Relative acidic compartment volume may be a useful biomarker to aid diagnosis, clinical monitoring, and evaluation of therapeutic responses in patients with LSDs.
Posted by Nicola Brunetti-Pierri, MD, FACMG