Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia.
BACKGROUND
Friedreich 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.


OBJECTIVE
To evaluate the performance of frataxin measurements as a diagnostic tool using two different immunoassays.


METHODS
Clinical 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.


RESULTS
For 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.


CONCLUSIONS
Frataxin 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.
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.
Eric C
EC
Deutsch
Department of Laboratory Medicine and Pathology, Department of Molecular Genetics, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Devin
D
Oglesbee
Department of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Nathaniel R
NR
Greeley
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.
David R
DR
Lynch
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D005621:Friedreich Ataxia / Q000097:blood / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D033862:Iron-Binding Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult; D000096923:Frataxin
D015415:Biomarkers; D033862:Iron-Binding Proteins; D000096923:Frataxin
MITOCHONDRIAL DISORDERS; MOVEMENT DISORDERS; PAEDIATRIC