• Eric C Deutsch, Devin Oglesbee, Nathaniel R Greeley, and David R Lynch.
• Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
• J. Neurol. Neurosurg. Psychiatr.. 2014 Sep 1;85(9):994-1002.

BackgroundFriedreich ataxia (FRDA) is a neurodegenerative disease caused by mutations in the frataxin (FXN) gene, resulting in reduced expression of the mitochondrial protein frataxin. Improved understanding of the pathophysiology of the disease has led to a growing need for informative biomarkers to assess disease progression and response to therapeutic intervention.ObjectiveTo evaluate the performance of frataxin measurements as a diagnostic tool using two different immunoassays.MethodsClinical and demographic information was provided through an ongoing longitudinal natural history study on FRDA. Frataxin protein levels from multiple cell types in controls, carriers and FRDA patients were measured and compared using a lateral flow immunoassay and a Luminex xMAP-based immunoassay. Receiver operating characteristic curve analyses were then performed to evaluate the sensitivity, specificity, and positive and negative predictive values for each immunoassay.ResultsFor whole blood and buccal cells, analysing FRDA patients and carriers together in a cohort resulted in higher sensitivities and positive predictive values compared with analyzing controls and carriers together, with similar results between each tissue type. We then compared the usefulness of a lateral flow immunoassay with a multianalyte Luminex xMAP-based immunoassay, and showed that both assays demonstrate high positive predictive values with low rates of false negatives and false positives.ConclusionsFrataxin measurements from peripheral tissues can be used to identify FRDA patients and carriers. While multiple cell types and assays may be useful for diagnostic purposes, each assay and cell type used has its advantages and disadvantages depending on study design and scope.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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