Our goal is to support the FA scientific, pharmaceutical and medical community with the tools necessary to execute their best work and improve patient outcomes.
FARA assists physicians and other healthcare providers treating individuals with Friedreich’s Ataxia (FA) by:
- Providing access to information about the diagnosis, management and treatment of FA
- Connecting them to FA specialists to help instruct best care management for patients
- Helping them get their patients registered in the FA patient registry
- Providing information on active and upcoming clinical trials
- Assisting with patient referrals to network centers running clinical trials
- Connecting newly diagnosed families to a community of support and hope
FARA wants to help you and your patients with diagnosis, participation in research, the latest results of clinical trials, and contacts with Friedreich ataxia clinicians.
· Primary symptoms at onset
- Ataxia – balance difficulty, decreased coordination
- Sensory loss (absent reflexes)
Onset of symptoms is often in childhood (frequently between ages of 5 and 15) and is usually associated with more rapid progression such as requiring a wheel chair by the teens or early twenties. Clinical manifestation after age 20 is considered late onset and does occur in later decades as well.
Information on diagnosis, clinical features, medical management and genetic counseling considerations is provided below:
Clinical Diagnosis
- Ataxia is the most common presenting symptom in early and late onset (loss of proprioception, absent reflexes).
- Cardiac features include non-specific T-wave abnormalities on EKG observed in almost all individuals and many individuals with left ventricular hypertrophy.
- Scoliosis is common at clinical presentation and pes cavus also presents early in disease.
- Family history – FA is autosomal recessive so often there is no other history ataxia in the family.
- Differential Diagnoses -- inherited Vitamin E deficiency, CoQ10 Deficiency, ataxia with oculomotor apraxia, spinocerebellar ataxias, multiple sclerosis.
Clinical Features
+ Neurological
- Loss of large sensory neurons (diminishing proprioception, balance, coordination and reflexes).
- Loss of spinocerebellar tracts (diminishing balance and coordination).
- Loss of dentate nucleus of the cerebellum (causing dysarthria, modest eye-movement abnormalities).
- Cerebellar cortex and cerebral cortex are spared, cognition is normal.
- MRI scans are normal or almost normal in early disease.
+ Cardiological
Hypertrophic cardiomyopathy can be progressive and severe, increasing morbidity and mortality. Dilated cardiomyopathy can develop in later disease. Clinically significant arrhythmias are also common. Clinically insignificant EKG abnormality (inverted T wave) is observed in nearly all individuals with FA.
+ Opthalmologic
Eye movements / fixation abnormalities are common (square-wave jerks, ocular flutter) findings. Optic atrophy is present in about 10% of patients.
+ ENT
Many individuals with FA have impaired auditory temporal processing resulting in significant hearing loss later in the disease course. Dysarthria is a prominent feature of FA at both early and late stages. Swallowing difficulty occurs in later-stage patients.
+ Other
Diabetes is present in 10-20% of patients and >65% have some degree of insulin resistance. Scoliosis is present in majority of patients (corrective surgery required in up to 50%). Urinary symptoms are common in adult patients (urgency, sphincter dyssennergia). Significant fatigue, impacting quality of life, is present in almost all patients.
+ Late Onset Friedreich Ataxia
Onset of symptoms is typically >20 years (range 20-60yrs; loss of coordination, ataxia). Progression is slower progression requiring assistance with ambulation; use of walker, scooter 10-15 years after diagnosis. Some individuals present with increased muscle tone, rigidity and spasticity. Retained reflexes has been observed in some. Dysarthria is less severe. MRI studies show cerebellar vermian atrophy in about 50% of individuals. Cardiomyopathy is rare. Individuals with gait and limb ataxias, dysarthria, loss of vibration sense, and fixational instability after age 25 years should be considered for molecular testing for GAA expansion in the FXN gene (late-onset patient typically has shorter GAA repeat on at least one allele; shortest observed in symptomatic individual ~65 repeats).
Medical Management - Proactive
There are no approved treatments for FA, however proactive medical management of symptoms and maintenance of good physical and emotional health improves health outcomes.
- Annual neurological exam; treat symptoms (e.g., baclofen for stiffness);
- Annual cardiac exam with ECHO and EKG and Holter; aggressive management of early features of heart failure; understanding of diastolic dysfunction;
- Annual x-rays of spine;
- Monitor blood glucose and hemoglobin A1C;
- Annual ophthalmology exam;
- Audiology screening (not just a routine audiogram but tests able to detect auditory processing impairment);
- Annual flu shot;
- Physical, occupational and speech therapy; preventive management of risks associated with neurological impairment.
Many physicians and individuals with FA consider vitamin and supplement regimens. Clinical studies have suggested modest or subjective benefit but none have been proven. Among those taken are Vitamin E, Co-enzyme Q10, and Idebenone.
Committed international physicians and researchers have critically evaluated medical literature, outcomes research and clinical practice for treating symptoms of FA, and have come together to prepare the first comprehensive Consensus Clinical Management Guidelines.
Effective October 1, 2020 – G11.11 – new diagnosis code for Friedreich's ataxia
A new diagnosis code has been approved for Friedreich’s ataxia by the Centers of Medicare and Medicaid Services (CMS). The new code, ICD-10 G11.11, is used by clinicians to document the FA diagnosis in medical records and is used by health insurance companies to determine coverage approval for claims.
Please Click Here to view a short video that explains the importance of updating your medical records with ICD-10 G11.11.
Click Here for a fact sheet for patients
Click Here for a fact sheet for clinicians
Genetic Diagnosis
Genetic testing is diagnostic in >98% of individuals. In more than 95% of abnormal alleles, the mutation is expansion of naturally occurring GAA repeat in first intron (non-coding region) of the frataxin or FRDA gene. GAA repeats: 3-33 – normal; 34-65 – premutation; 66-1700 - abnormal. Less than 5% of abnormal alleles have point mutations in the coding or regulatory regions of the gene. GAA repeat expansion sizes correlate with measures of disease severity; disease-range expansions diminish but do not eliminate frataxin expression.
Genetic testing should be performed by an accredited laboratory. GeneTests Web site, a publicly funded medical genetics information resource developed for physicians, other healthcare providers, and researchers, available at no cost. GeneTests hosts an international database of genetic testing laboratories.
Genetic Counseling Considerations
Genetic testing results in ~98% detection in symptomatic individuals. In rare cases, analysis of frataxin protein levels can be helpful to confirming or ruling out a diagnosis.
FA is an autosomal recessive disorder with prevalence of approximately 1 in 50,000 in populations of European origin. Approximately 1 in 90 in those populations are heterozygous carriers of an abnormal FXN allele. Carrier testing is recommended for anyone with a positive family history of Friedreich ataxia and for partners of known carriers. Presymptomatic testing for at-risk siblings/relatives is available, however genetic counseling is strongly recommended to assist individuals/families in considering the risks vs benefits for testing an untreatable genetic condition.
Are your Friedreich ataxia patients ready for clinical trial?
New therapies for Friedreich Ataxia are in clinical trials with encouraging results and giving real hope for patients today. Individuals with FA should enroll online in FARA's patient registry at http://www.curefa.org/patient-registry.
This is a simple online registry that individuals can complete themselves, however it is helpful if individuals have a copy of their genetic test results so that they are able to enter information about confirmation of diagnosis.
Participation in this registry will ensure that they will receive a recruitment notice for any trial for which they appear to be eligible.
Would you like to contact an experienced Friedreich ataxia clinician near you?
The Collaborative Clinical Research Network in Friedreich's Ataxia (CCRN in FA) is an international network of clinical research centers that work together to advance treatments and clinical care for individuals with FA. The CCRN in FA can assist you in offering your patients access to clinical research studies in FA. The investigators and coordinators at each of the sites can work with you to provide guidance on updates in clinical care and management for your patients.
For contact information for clinicians who see a number of Friedreich ataxia patients and are familiar with the clinical research and development, please see http://www.curefa.org/network.html.
Would you like information on the therapeutic pipeline and clinical trials in Friedreich ataxia?
Please see http://www.curefa.org/pipeline.html.
Sanjay I Bidichandani, MBBS, PhD
Martin B Delatycki, MBBS, FRACP, PhD
