Friedreich Ataxia, Frataxin, Quantitative, Blood Spot
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Friedreich ataxia (FA) is an autosomal recessive disease affecting approximately 1:50,000 Caucasians. The disease is clinically characterized by progressive spasticity, ataxia, dysarthria, absent lower limb reflexes, sensory loss, and scoliosis. Hypertrophic cardiomyopathy is present in approximately two-thirds of patients and is the most frequent cause of premature death in individuals with FA. Although most individuals begin experiencing initial symptoms between 10 and 15 years of age, atypical late-onset forms with initial symptoms presenting after age 25 do occur.
FA is caused by mutations in the FXN gene encoding a mitochondrial protein, frataxin. Mutations in this gene lead to a reduced expression of frataxin, which causes the clinical manifestations of the disease. Approximately 98% of individuals with FA have a homozygous expansion of the GAA trinucleotide repeat in intron 1 of FXN. The remaining 2% of FA patients have the trinucleotide expansion on 1 allele and a point mutation or deletion on the second allele. Normal alleles contain between 5 to 33 GAA repeats. Disease-causing alleles typically range from 66 to 1,700 repeats, though the majority of individuals with FA have repeats ranging from 600 to 1,200.
Historically, FA has been diagnosed by use of a DNA-based molecular test to detect the presence of the GAA expansion. Unfortunately, testing for the triplet repeat expansion will miss those patients with point mutations or deletions. Moreover, a molecular-based analysis is not able to effectively monitor treatment, is not amenable to multiplexing with other disease analytes, nor can it be efficiently utilized for population screening. In contrast, a protein-based assay measuring concentration of frataxin is suitable for both diagnosis as well as treatment monitoring in individuals with FA.
Diagnosing individuals with Friedreich ataxia in blood spot specimens
Monitoring frataxin levels in patients with Friedreich ataxia
Normal results (> or =15 ng/mL for pediatric and > or =21 ng/mL for adult patients) in properly submitted specimens are not consistent with Friedreich ataxia.
For results outside the normal reference range an interpretative comment will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not suitable for carrier detection.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Pediatric (<18 years) normal frataxin: > or =15 ng/mL
Adults (> or =18 years) normal frataxin: > or =21 ng/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Deutsch EC, Oglesbee D, Greeley NR, Lynch DR: Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia. J Neurol Neurosurg Psychiatry 2014 Sep;85(9):994-1002
2. Babady NE, Carelle N, Wells RD, et al: Advancements in the pathophysiology of Friedreich ataxia and new prospects for treatments. Mol Genet Metab 2007;92:23-35