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Friedreich Ataxia: Differential Diagnoses & Workup

Author: Stephen Kishner, MD, MHA, Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans
Contributor Information and Disclosures

Updated: Aug 21, 2009

Differential Diagnoses

Other Problems to Be Considered

Hereditary motor and sensory neuropathy (HMSN) type 1

Abetalipoproteinemia

Isolated vitamin E deficiency

Other early onset ataxias (ie, Marinesco-Sjögren syndrome, Ramsay Hunt syndrome, X-linked inherited ataxia)

Late-onset ataxias (ie, common autosomal dominant cerebellar ataxia [ADCA], Machado-Joseph disease, Cuban and other forms of ADCA, Sporadic cerebellar ataxia of late onset)

Ataxia telangiectasia

Developmental ataxias (ie, Dandy-Walker syndrome and Chiari malformation, Joubert syndrome, Gillespie syndrome)

Acquired ataxias (ie, trauma, infections [eg, viral including Epstein-Barr virus, echovirus, coxsackievirus, polio virus, Creutzfeldt-Jakob disease, AIDS, toxoplasmosis, Lyme disease, mycoplasma, legionellosis, bacterial abscess], vascular, neoplasms, neoplastic syndromes, demyelinating, metabolic [eg, hyponatremia, hypothyroidism, nutritional], toxins [eg, anticonvulsants, lithium, bismuth, cytotoxic drugs, solvents, methyl mercury, alcohol-related cerebellar degeneration], physical agents [eg, heatstroke])

Workup

Laboratory Studies

  • The diagnosis of FA essentially is a clinical one.
  • Confirmation of the diagnosis by DNA testing is recommended for all patients in whom FA is clinically suspected.10
    • The polymerase chain reaction with nucleotide primers spanning the repeated region is used to amplify the DNA in intron 1. The products then are fractionated on an agarose or polyacrylamide gel.
    • On normal chromosomes, the number of GAA repeats varies from 7-22 units, whereas on disease chromosomes, the range varies from approximately 100-2000 repeats. A normal-sized repeat length on both chromosomes argues strongly against a diagnosis of FA.

Imaging Studies

  • CT scan and MRI findings are normal or show mild cerebellar atrophy (usually observed late in the disease). The cervical spinal cord often is atrophied.
  • Echocardiogram exhibits evidence of hypertrophic cardiomyopathy in approximately 40% of patients. The severity of left ventricular hypertrophy is related to the number of GAA repeats.

Other Tests

  • Electrocardiogram is abnormal in approximately two thirds of patients, most distinctively with widespread T-wave inversion. If this is present in this context, it is virtually diagnostic of FA.
  • Electromyography (EMG) and nerve conduction study (NCS): Electrodiagnostic findings that support the diagnosis of FA include the following:
    • Median motor conduction velocity of greater than 40 milliseconds; absent or reduced amplitude of sensory nerve action potential
    • Absent H-reflex
    • Abnormal central motor conduction time after transcranial
      magnetic stimulation

Histologic Findings

Morphology

The spinal cord exhibits loss of axons and gliosis in the posterior columns, the distal portions of corticospinal tracts, and the spinocerebellar tracts. Degeneration of neurons is present in the spinal cord (Clarke column), brain stem (cranial nerve nuclei VIII, X, and XII), cerebellum (dentate nucleus and the Purkinje cells of the superior vermis), and, to some extent, the Betz cells of the motor cortex.

Large dorsal root ganglion neurons also are decreased in number, their large myelinated axons traveling first in the dorsal root ganglion and then in dorsal columns, thereby undergoing secondary degeneration. The heart is enlarged and may have pericardial adhesions. Multifocal destruction of myocardial fibers with inflammation and fibrosis is detectable in about one half of the patients who come to autopsy examination.

More on Friedreich Ataxia

Overview: Friedreich Ataxia
Differential Diagnoses & Workup: Friedreich Ataxia
Treatment & Medication: Friedreich Ataxia
Follow-up: Friedreich Ataxia
References
Further Reading
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References

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Keywords

Friedreich ataxia, Friedreich's ataxia, FA, progressive ataxia, hereditary spinal ataxia, heredotaxia

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Contributor Information and Disclosures

Author

Stephen Kishner, MD, MHA, Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans
Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

Medical Editor

Jegan Krishnan, MBBS, FRACS, PhD, Professor, Chair, Department of Orthopedic Surgery, Flinders University of South Australia; Senior Clinical Director of Orthopedic Surgery, Repatriation General Hospital; Private Practice, Orthopaedics SA, Ashford Specialist Centre
Jegan Krishnan, MBBS, FRACS, PhD is a member of the following medical societies: Australian Medical Association, Australian Orthopaedic Association, and Royal Australasian College of Surgeons
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Paul E Di Cesare, MD, FACS, Chair and Professor, Department of Orthopedic Surgery, University of California Davis School of Medicine
Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Sigma Xi
Disclosure: stryker Consulting fee Consulting

CME Editor

Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital
Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Harris Gellman, MD, Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society
Disclosure: Nothing to disclose.

 
 
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