The effects of vitamin K1 administration in Pseudoxanthoma elasticum patients. A pilot study

Tuesday, 31 July, 2018

Why was Pseudoxanthoma elasticum studied?

Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene encoding multidrug resistance-associated protein 6 (MRP6). The disease is characterised by progressive calcification and loss of function of elastic fibres causing central blindness, skin papules, and vascular calcification. Several hypotheses have been postulated and, due to its involvement in regulation of vascular calcification, it has been suggested that vitamin K may be involved. However the disease pathogenesis is not yet completely understood. In this study, patients affected by PXE were compared to PXE carriers and non-carriers. The aim was to look at baseline levels of vitamin K-dependent proteins and vitamin K metabolites and to determine whether parenteral administration of phytomenadione (vitamin K1) was effective in altering their circulatory concentrations.

Methodology used

Patients and healthy controls were compared:

- Eight PXE patients with typical clinical symptoms (skin, retinal, and vascular calcification) and two with ABCC6 causative mutations

- Thirteen clinically unaffected first-degree patients’ relatives (9 carrying one ABCC6 mutation and 4 non-carriers).

For this study serum vitamin K, urinary vitamin K metabolites and vitamin K dependent proteins (serum carboxylated and undercarboxylated osteocalcin, Gas6 and undercarboxylated prothrombin (PIVKA-II)) were assessed at baseline and after 1 and 6 weeks post treatment with vitamin K1 (10 mg IM).

Summary of the results

The comparison of PXE patients, heterozygotes and non-carriers revealed differences in baseline concentrations of serum vitamin K2 (MK-4) and of urinary vitamin K metabolites. The response of circulating vitamin K-dependent proteins to vitamin K1 administration was similar in all groups.


The study showed that the physiological axis between vitamin K1 and vitamin K-dependent proteins is preserved. However, differences in the concentrations of vitamin K metabolites and of MK-4 suggest that vitamin K metabolism could be altered in PXE patients. Further studies are required to establish to what extent vitamin K metabolism is altered and the cause of this biochemical anomaly. 

The full report can be found at:

Carrillo-Linares JL, García-Fernández MI, Morillo MJ, Sánchez P, Rioja J, Barón FJ, Ariza MJ, Harrington DJ, Card D, Boraldi F, Quaglino D, Valdivielso P. The Effects of Parenteral K1 Administration in Pseudoxanthoma Elasticum Patients Versus Controls. A Pilot Study. Frontiers in Medicine 2018; 5:86.

For further information, please contact

Dr Dominic Harrington: 
Dominic [dot] Harrington [at] viapath [dot] co [dot] uk

David Card: 
David [dot] Card [at] viapath [dot] co [dot] uk