Friedreich's Ataxia FRDA

1
Friedreich's Ataxia (FRDA)
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Historical1

• First Described by Nicholaus Friedreich, 1863
• First hereditary ataxia to be distinguished
• Autosomal recessive
• Prevalence 150,000
• Onset 8-15 yrs

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Core presenting symptoms2

• Gait Ataxia most common
• Dysarthria
• Areflexia (generally at ankle)
• Pyramidal weakness of the legs
• extensor plantar responses
• Distal loss of joint position
• Distal loss of vibration sense

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Other Symptoms

• Cardiomyopathy
• As high as 90 have abnormalities, clinical,
  significance variable
• Skeletal abnormalities
• scoliosis (85)
• foot deformities (pes cavus, pes planus and
  equinovarus)
• optic atrophy (25)
• Diabetes (10)
• Deafness (lt 10)

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Genetics3

• Marker
• Expansion Carrier
• normal "heterozygote
• Expansion Carrier
• Effected
• Effected
• Homozygote

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Genetics (Continued)

• First autosomal recessive condition due to a
  dynamic repeat (1988)
• Triplet GAA repeat in chromosome 9q13, 100 to
  2000 repeats
• Normal 7 to 22
• Repeat located in 1st intron
• Leads to improper splicing and reduced levels of
  frataxin
• Thought to be a mitochondrial iron transporter

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Treatment

• No curative treatment
• Treatment of symptoms and accompanying
  complications only
• Vitamin E and other antioxidants
• From vitamin E malabsorption patients with
  similar spinocerebellar syndrome

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References

• NINDS. Friedreich's Ataxia Fact Sheet.
  http//www.ninds.nih.gov/disorders/friedreichs_ata
  xia/detail_friedreichs_ataxia.htm69483070
• Jerry Kaplan. Friedreichs ataxia is a
  mitochondrial disorder. Proc. Natl. Acad. 1999
  961094810949
• Wood. N. Diagnosing Friedreich's ataxia. Arch Dis
  Child 199878204-207
• Friedreich's Ataxia Parents Group.
  http//www.fortnet.org/fapg/