Feasibility of cellular bioenergetics as a biomarker in porphyria patients

Porphyria is a group of metabolic disorders due to altered enzyme activities within the heme biosynthetic pathway. It is a systemic disease with multiple potential contributions to mitochondrial dysfunction and oxidative stress. Recently, it has become possible to measure mitochondrial function from cells isolated from peripheral blood (cellular bioenergetics) using the XF96 analyzer (Seahorse Bioscience). Mitochondrial respiration in these cells is measured with the addition of activators and inhibitors of respiration. The output is measured as the O(2) consumption rate (OCR) at basal conditions, ATP linked, proton leak, maximal, reserve capacity, non-mitochondrial, and oxidative burst. We performed cellular bioenergetics on 22 porphyria (12 porphyria cutanea tarda (PCT), seven acute hepatic porphyria (AHP), and three erythropoietic protoporphyria (EPP)) patients and 18 age and gender matched healthy controls. Of porphyria cases, eight were active (2 PCT, 1 EPP, and 5 AHP) and 14 in biochemical remission. The OCR were decreased in patients compared to healthy controls. The bioenergetic profile was significantly lower when measuring proton leak and the non-mitochondrial associated OCR in the eight active porphyria patients when compared to 18 healthy controls. In conclusion, we demonstrate that the bioenergetic profile and mitochondrial activities assessed in porphyria patients and is different than in healthy control individuals. Further, our novel preliminary findings suggest the existence of a mitochondrial dysfunction in porphyria and this may be used as potential non-invasive biomarker for disease activity. This needs to be assessed with a systematic examination in a larger patient cohort. Studies are also suggested to examine mitochondrial metabolism as basis to understand mechanisms of these findings and deriving mitochondrial based therapies for porphyria.