AUTHOR=Carrillo-Linares Juan Luis , García-Fernández María Inmaculada , Morillo María José , Sánchez Purificación , Rioja José , Barón Francisco Javier , Ariza María José , Harrington Dominic J. , Card David , Boraldi Federica , Quaglino Daniela , Valdivielso Pedro TITLE=The Effects of Parenteral K1 Administration in Pseudoxanthoma Elasticum Patients Versus Controls. A Pilot Study JOURNAL=Frontiers in Medicine VOLUME=5 YEAR=2018 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2018.00086 DOI=10.3389/fmed.2018.00086 ISSN=2296-858X ABSTRACT=Introduction

Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene. Vitamin K1 is involved in the posttranslational carboxylation of some proteins related to inhibition of the calcification process. Our aim was to investigate, in patients affected by PXE, baseline levels of vitamin K1-dependent proteins and -metabolites and whether parenteral administration of phytomenadione was effective in modulating their levels.

Methods

We included eight PXE patients with typical clinical symptoms (skin, retina, and vascular calcification) and two ABCC6 causative mutations; 13 clinically unaffected first-degree patients’ relatives (9 carrying one ABCC6 mutation and 4 non-carriers). We assessed urinary vitamin K1 metabolites and serum Glu- and Gla-OC, Gas6 and undercaboxylated prothrombin (PIVKA-II), at baseline and after 1 and 6 weeks after a single intramuscular injection of 10 mg vitamin K1.

Results

Comparison of PXE patients, heterozygous, and non-carriers revealed differences in baseline levels of serum MK-4 and of urinary vitamin K metabolites. The response to phytomenadione administration on vitamin K-dependent proteins was similar in all groups.

Conclusion

The physiological axis between vitamin K1 and vitamin K-dependent proteins is preserved; however, differences in the concentration of vitamin K metabolites and of MK-4 suggest that vitamin K1 metabolism/catabolism could be altered in PXE patients.