Friedreich’s ataxia diagnostic process and criteria

Last updated March 4, 2024, by Lindsey Shapiro, PhD
Medically reviewed by David Lynch, MD, PhD

A diagnosis of Friedreich’s ataxia (FA) is largely reached through a comprehensive physical and neurological examination, supported by MRI, laboratory workups, and occasionally electrodiagnostic tests. A definitive diagnosis can be reached through genetic testing.

Presenting symptoms

Most FA patients present with a neurological complaint, typically progressive gait unsteadiness, in childhood or adolescence (ages 5-15). Complaints may also include general clumsiness and tripping, falls, or declines in athletic performance and an inability to keep up with peers in motor skills. Evidence of ataxia generally emerges after early motor milestones are achieved.

Atypical presentations

Fewer than 10% of patients will present with non-neurological symptoms at onset. Scoliosis is the most common, seen particularly in patients between ages 10 and 20. Cardiomyopathy may rarely be the presenting symptom.

Individuals with late-onset FA (onset after age 25) or very late-onset (after age 40) typically present with classic neurological symptoms, but atypical symptoms such as spasticity and retained reflexes are more common.

Current diagnostic guidelines and process

Prior to the availability of genetic testing, various sets of clinical diagnostic criteria were developed for diagnosing FA. Shared features included onset before age 20-25, progressive ataxia, and lower limb areflexia. However, while diagnostic criteria have high positive predictive value for FA, their sensitivity tends to be low.

Genetic testing is the definitive way to diagnose FA and rule out differential diagnoses, supported by findings from a comprehensive neurological workup. MRI, electromyography, nerve conduction studies, and blood tests are not usually necessary in a patient with typical presentation in whom genetic testing is readily available. The existence of treatments for FA now demand that definitive diagnosis (through genetic testing) be performed expeditiously.

Physical exam

Early identification of FA relies heavily on a thorough physical and neurological workup, as well as the medical history, of patients presenting with symptoms of ataxia or spinal deformities.

Important observations in medical history:

• Complaints of gait unsteadiness or clumsiness in first decade or early second decade of life
• Normal achievement of early motor milestones
• Family history possible with large sibships or consanguineous families; most will not have family history due to the disease’s autosomal recessive inheritance pattern.

In physical and neurological examination:

• Stance and gait changes (particularly in children older than 10 years)
  • Difficulty with single leg stance, tandem stance, feet together stance, or standing with eyes closed
  • Broadening of stance to maintain balance
  • Increase in inter-foot distance with walking
• Lower limb ataxia
  •  heel to shin slide reveals a side-to-side oscillation of the heel on the shin bone
• Sensory neuropathy (though usually asymptomatic)
  • Deep tendon reflex loss in lower limbs is virtually universal
  • Impaired position sense possible
  • Significant sensory neuropathy may be lacking in late-onset patients
• Subtle oculomotor signs indicative of cerebellar disease can be present, including inaccurate saccades, jerky pursuit, or square wave jerks. Nystagmus is not typical.

Spasticity and muscle weakness are not typical as presenting symptoms in FA patients, although spasticity may be more common in late-onset FA. No Gowers sign is observed. Cognition is typically preserved without learning disabilities.

Genetic testing

Genetic testing provides the final FA diagnosis. The GAA repeat expansion, found in at least one allele of the FXN gene of all FA patients, cannot be detected by next generation sequencing technology, but commercial testing panels are available for direct sizing of the GAA repeat. Patients with ataxia who have only one expanded allele should have the other allele sequenced for point mutations.

Other tests

In patients of typical age of onset with a slowly progressive ataxia with symmetric findings, genetic testing can be the initial test. In others, further testing can be included early in the evaluation.

Brain and spinal cord MRIs are usually normal at the time of diagnosis, without overt cerebellar atrophy despite ataxia. Volumetric data can suggest spinal cord atrophy, but this may be difficult to detect in clinical scans. An MRI can also rule out other causes of ataxia.

Electrodiagnostic testing indicates sensory axonal neuropathy with loss or greatly diminished sensory nerve action potential amplitudes. Findings are particularly striking in children as they usually have robust sensory nerve responses. Motor nerve conductions are typically normal and do not reveal conduction velocities in the demyelinating range.

More than 70% of FA patients have subtle and nonspecific electrocardiogram abnormalities such as ST segment changes and T wave inversions. Echocardiograms may show hypertrophic cardiomyopathy. FA should be considered in children with early-onset cardiomyopathy.

Blood tests may also be used to rule out differential diagnoses. Serum muscle enzymes are found to be normal in FA, as are vitamin E levels.

Referral process

In most cases of childhood onset, initial complaints of neurological or orthopedic problems are first addressed by a patient’s primary pediatrician, with subsequent referrals to a neurologist or orthopedic surgeon. All these physicians should be familiar with FA as a possible diagnosis in patients presenting with motor difficulties or spinal deformities. 

Where idiopathic scoliosis is the presenting symptom, some element of a neurological exam should be performed. Any evidence of motor disability progression should prompt consultations or referrals to a neurologist.

Next: Differential diagnosis