Friedreich ataxia (FRDA) is characterized by slowly progressive ataxia, typically arising in late childhood or early adolescence. Common features include dysarthria, muscle weakness, spasticity in the lower limbs, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense. Cardiomyopathy and diabetes mellitus are relatively common.

FRDA is an autosomal recessive condition caused by biallelic pathogenic variants of the frataxin (FXN) gene on chromosome 9q13.  Approximately 95% of patients with Friedreich ataxia are homozygous for an FXN GAA-repeat expansion; the remaining patients are compound heterozygotes for an FXN GAA-repeat expansion and either an inactivating point mutation or deletion of FXN.  To date, no affected individuals with two non-GAA triplet repeat mutations have been reported.

GAA repeat lengths are classified according to their phenotypic expression:

• Normal alleles: 5 – 33 repeats
• Mutable normal allels: 34 – ~65 repeats

The exact boundary between normal and full penetrance alleles has not been determined; alleles at the boundary are assessed further.

• Full penetrance (expanded) alleles: ~66 repeats or greater

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of Friedreich Ataxia.
2. Carrier testing:
   1. Adults at risk to be carriers because of a family history of FRDA.
3. Prenatal testing: (technically feasible, but rarely performed – contact MGL to discuss):
   1. Pregnancies known to be at risk of FRDA and the mutations are known.
4. Presymptomatic testing:
   1. Requests to test asymptomatic children who are at risk of developing FRDA are only accepted following genetic counselling by a recognized genetic service.

PCR and triplet-primed (tp) PCR amplification is performed across the GAA repeat region of the FXN gene to assess for normal and expansion allelles.  

For more information, see FAQ

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

In certain scenarios of repeat size mosaicism, false negative results may occur. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.