P21

ASSESSING THE MITOCHONDRIAL IRON METABOLISM IN HEREDITARY HEMOCHROMATOSIS

Sonia Distante1,*, Ragnhild Skinnes1, Kari Høie1, Lars Mørkrid1, Lars Eide1

1Medical biochemistry, Oslo University Hospital, Oslo, Norway

Introduction: In hemochromatosis, diagnosis and assessment of treatment is based on transferrin saturation / ferritin level. Here, we evaluated lymphocyte mitochondrial iron as putative markers for hemochromatosis and treatment

Objectives: 1. To evaluate the use of mitochondrial iron proteins from easily accessible lymphocytes to evaluate pathology of hemochromatosis and subsequent effect of venesectio therapy. 2. Assess mitochondrial iron metabolism and investigate how this is altered in hemochromatosis

Methods: Patients (n=12) from the hemochromatosis outpatient clinic were sequentially recruited to this study. They were either homozygous for the HFE C282Y mutation or compound heterozygous C282Y/H63D and had raised iron parameters. Lymphocytes from EDTA blood were isolated from the patients and age/sex matched controls, and the following mitochondrial iron proteins were quantified by western analysis:  Frataxin, mitochondrial Ferritin, Mitoferrin, MnSOD, IscU1/2, Iba57 and ALAS1.

Results: Lymphocytes from untreated hemochromatosis patients have significantly higher levels mitochondrial ferritin whereas the levels of the other proteins were similar to controls. Venesectio therapy did not alter mitochondrial ferritin, but significanly increased the level of MnSOD and reduced the level of IscU1/2. Furthermore, normal mitochondrial iron metabolism is characterized by a positive correlation between MnSOD and Iba57, as well as a negative correlation between Mitoferrin and Iba57, and Mitoferrin and MnSOD. This correlation is abrogated in hemochromatosis, where Frataxin correlates negatively with mitoferrin

Conclusion: Lymphocytes from hemochromatosis patients seems to provide a suitable model for studying the effect of systemic to mitochondrial iron metabolism before and after venesectio. Our results imply that the effect of venesectio can be ascribed to gain of effect rather than reversal of defect on mitochondrial iron metabolism

Keywords: Biomarker development, Blood, Inborn error of metabolism