Friedreich ataxia


00:00 / 00:00



Friedreich ataxia


Central nervous system disorders

Spina bifida

Chiari malformation

Dandy-Walker malformation


Tethered spinal cord syndrome

Aqueductal stenosis

Septo-optic dysplasia

Cerebral palsy

Spinocerebellar ataxia (NORD)

Transient ischemic attack

Ischemic stroke

Intracerebral hemorrhage

Epidural hematoma

Subdural hematoma

Subarachnoid hemorrhage

Saccular aneurysm

Arteriovenous malformation

Broca aphasia

Wernicke aphasia

Wernicke-Korsakoff syndrome

Kluver-Bucy syndrome

Concussion and traumatic brain injury

Shaken baby syndrome


Febrile seizure

Early infantile epileptic encephalopathy (NORD)

Tension headache

Cluster headache


Idiopathic intracranial hypertension

Trigeminal neuralgia

Cavernous sinus thrombosis

Alzheimer disease

Vascular dementia

Frontotemporal dementia

Lewy body dementia

Creutzfeldt-Jakob disease

Normal pressure hydrocephalus


Essential tremor

Restless legs syndrome

Parkinson disease

Huntington disease

Opsoclonus myoclonus syndrome (NORD)

Multiple sclerosis

Central pontine myelinolysis

Acute disseminated encephalomyelitis

Transverse myelitis

JC virus (Progressive multifocal leukoencephalopathy)

Adult brain tumors

Acoustic neuroma (schwannoma)

Pituitary adenoma

Pediatric brain tumors

Brain herniation

Brown-Sequard Syndrome

Cauda equina syndrome

Treponema pallidum (Syphilis)

Vitamin B12 deficiency


Friedreich ataxia

Neurogenic bladder


Neonatal meningitis


Brain abscess

Epidural abscess

Cavernous sinus thrombosis

Creutzfeldt-Jakob disease

Central and peripheral nervous system disorders

Sturge-Weber syndrome

Tuberous sclerosis


von Hippel-Lindau disease

Amyotrophic lateral sclerosis

Peripheral nervous system disorders

Spinal muscular atrophy


Guillain-Barre syndrome

Charcot-Marie-Tooth disease

Trigeminal neuralgia

Bell palsy

Winged scapula

Thoracic outlet syndrome

Carpal tunnel syndrome

Ulnar claw

Erb-Duchenne palsy

Klumpke paralysis


Myasthenia gravis

Lambert-Eaton myasthenic syndrome

Autonomic nervous system disorders

Orthostatic hypotension

Horner syndrome

Nervous system pathology review

Congenital neurological disorders: Pathology review

Headaches: Pathology review

Seizures: Pathology review

Cerebral vascular disease: Pathology review

Traumatic brain injury: Pathology review

Spinal cord disorders: Pathology review

Dementia: Pathology review

Central nervous system infections: Pathology review

Movement disorders: Pathology review

Neuromuscular junction disorders: Pathology review

Demyelinating disorders: Pathology review

Adult brain tumors: Pathology review

Pediatric brain tumors: Pathology review

Neurocutaneous disorders: Pathology review


Friedreich ataxia


0 / 8 complete

USMLE® Step 1 questions

0 / 2 complete

High Yield Notes

10 pages


Friedreich ataxia

of complete


USMLE® Step 1 style questions USMLE

of complete

A 10-year-old girl is brought to her primary care physician with worsening gait instability. Over the past few weeks, the patient has had several falls at school. Her mother has noticed that the patient’s gait appears uncoordinated and that she has occasionally been slurring her words. The patient’s physical exam is notable for high-arched feet, difficulty walking in a straight line, and decreased vibratory sensation in both the upper and lower extremities. She subsequently undergoes a genetic analysis, which demonstrates a GAA repeat on chromosome 9. Which of the following is the most common cause of mortality in individuals with this disease process? 

External References

First Aid








Autosomal recessive disease

Friedreich ataxia p. 549

Diabetes mellitus p. 352-360

Friedreich ataxia p. 549

Dysarthria p. 533

Friedreich ataxia as p. 549

Friedreich ataxia p. 549

chromosome association p. 62

hypertrophic cardiomyopathy p. 317

inheritance of p. 60

mechanism of p. 60

Gait disturbance

Friedreich ataxia p. 549


Friedreich ataxia p. 549

Pes cavus

Friedreich ataxia p. 549


Friedreich ataxia p. 549



Evan Debevec-McKenney

Jessica Reynolds, MS

Friedreich’s ataxia is a disorder where there is impaired mitochondrial function that results in damage to various organ systems. In particular, the nervous system gets damaged which causes ataxia, where the muscles cannot be moved in a coordinated way. The disorder also affects other organs like the heart and pancreas. The disease gets its name from the German physician Nikolaus Friedreich who first described the disease over 150 years ago.

So, normally on chromosome 9, there’s a gene called the FXN gene that encodes a mitochondrial protein called frataxin. The normal amount of frataxin varies by tissue, with some tissues like the nervous system, pancreas, and heart, containing lots of it. Frataxin helps put together cofactors called iron-sulfur clusters. It is a combination of iron and sulfur that form part of enzymes with many functions such as electron transfer, a key part of mitochondrial ATP production.

Friedreich’s ataxia is caused by a mutation in the FXN gene where there is an abnormal repetition of a GAA sequence within that gene. This is called a triplet repeat, or trinucleotide repeat, which means that a group of three DNA nucleotides is repeated multiple times in a row, in this case guanine, adenine, and adenine. Normally, the GAA sequence is repeated 7 to 34 times within the FXN gene. But, in Friedreich’s ataxia there is repeat expansion where there are 100 to 1700 times as many copies, with most individuals having repeats ranging from 600 to 1200 times.

Now, Friedreich’s ataxia is inherited as an autosomal recessive condition. It’s passed on by parents who are “carriers” because they have one expanded FXN gene and one normal FXN gene, but don’t have any symptoms of Friedreich ataxia. They end up passing on their expanded FXN genes to their kid. Inheriting both copies of the FXN gene with an expanded GAA repeat is the most common way to get Friedreich’s ataxia.

The repeat expansion causes gene silencing which is when the FXN gene is not transcribed normally and very little frataxin protein is made. With low levels of frataxin, the mitochondria are unable to efficiently incorporate iron into iron-sulfur clusters and as a result, there is lower mitochondrial ATP production, so there’s less energy available for the cell. Furthermore, iron accumulates inside the mitochondria which reacts with oxygen to create unstable oxygen radicals. Over time these free radicals damage DNA and proteins in the cells in a process called oxidative damage. Then, this energy deficiency and oxidative damage result in dysfunction and death of cells that are highly dependent on mitochondrial function such as neurons, cardiomyocytes and pancreatic beta cells. The loss of neurons leads to ataxia. In the heart, there is abnormal thickening of the ventricles, a condition called hypertrophic cardiomyopathy, which is the most common cause of death in people with Friedreich’s ataxia.


Copyright © 2023 Elsevier, except certain content provided by third parties

Cookies are used by this site.

USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME). COMLEX-USA® is a registered trademark of The National Board of Osteopathic Medical Examiners, Inc. NCLEX-RN® is a registered trademark of the National Council of State Boards of Nursing, Inc. Test names and other trademarks are the property of the respective trademark holders. None of the trademark holders are endorsed by nor affiliated with Osmosis or this website.