E-Poster Presentation ESA-SRB-ANZBMS 2021

Background: Fabry disease (FD) is a genetic disorder caused by mutations in GLA, the X-linked gene encoding α-Galactosidase A. Deficient enzyme activity leads to the build-up of lysosomal contents, contributing directly or indirectly to multiple pathologies centered mostly on the kidney, heart, and central nervous system, but patients often also experience osteopenia or osteoporosis.

The liver-derived glycoprotein fetuin-A stabilizes calcium and phosphate in extracellular fluid by forming colloidal mineral-protein complexes, calciprotein particles (CPP), which facilitate the stabilization, transport and clearance of excess mineral from the circulation. While most CPP circulate as monomers, they combine to form spheroidal primary CPP (CPP-I) and larger, elongated secondary CPP (CPP-II), both of which are associated with vascular and renal pathology when present at high levels.

Methods: We measured the serum CPP-I and CPP-II levels of 59 individuals with Fabry disease (63% female; mean age 45 ± 13) by flow cytometry and compared them to measurements of bone mineral density (BMD) and serum biochemistry, adjusting for demographics, comorbidities, and medications.

Results and Conclusions: We found that low BMD at the total hip and femoral neck was associated with high levels of CPP, in particular CPP-II (Table 1), and this relationship was weakly associated with male sex but independent of kidney function. This is the first time sex differences in CPP levels have been observed, and it is probably due to the X-linked nature of the disease, since both low BMD and high CPP may be markers of more severe disease in these individuals. The co-occurrence of these phenomena implies a direct relationship linking the bone and CPP systems, which merits further investigation to establish if it is unique to FD or a more generalized association.