Assessment of cell-free levels of iron and copper in patients with Friedreich's ataxia

摘要

Friedreich's ataxia (FRDA), a progressive neurodegenerative disorder caused by trinucleotide (GAA) repeat expansion in frataxin (fxn) gene which results in decreased levels of frataxin protein. Insufficient frataxin levels leads to iron and copper deposits in the brain and cardiac cells. A total of hundred and twenty patients, suspected of FRDA were screened for the (GAA) repeats in the fxn gene and only confirmed patients (n=25) were recruited in the study. The total Iron and total copper concentrations were measured in blood plasma using Nitro PAPS and Dibrom PAESA method, respectively both in patients and age, sex matched healthy controls. The iron levels mean +/- SD (6.2 +/- 3.8) in plasma of FRDA patients were found to be significantly decreased as compared to healthy controls mean +/- SD (15.2 +/- 4.2). A similar trend was observed in case of plasma copper levels in FRDA patient (8.15 +/- 4.6) as compared to controls (17.5 +/- 3.40). Present results clearly prove abnormal distribution of extra-cellular iron in FRDA patients, which is in accordance with the well established fact of intracellular iron overload, which is the key feature of the pathogenesis of this disease. This can be of importance in understanding the pathophysiology of the disease in association with frataxin/iron. It appears that intracellular sequestration of trace metals in FRDA patients (due to low frataxin) results in their sub-optimal levels in blood plasma (extra-cellular) an observation that can find prognostic application in clinical trials.