Friedreich’s Ataxia (FRDA)

About Friedreich’s Ataxia (FRDA)

• Friedreich’s ataxia (FRDA) is a genetic disorder that progressively damages the nerves and heart.
• Caused by: It is caused by a mutation in the Frataxin (FXN) gene, which reduces the production of frataxin, a protein essential for mitochondria.
• Genetic Mechanism:
  • Normal variants: The FXN gene normally contains 5–11 or 12–33 repeats of a particular DNA sequence.
    • These are called short-normal and long-normal variants.
  • Expanded variants: In people with FRDA, the same sequence is repeated 100–1,500 times. These are called expanded variants.
  • Reduced frataxin: The large number of repeats changes the chromosome into a closed structure, which reduces the production of frataxin.
  • Cell damage: Low frataxin makes mitochondria less effective at producing ATP and causes toxic by-products to accumulate, making cells dysfunctional.
  • Inheritance: FRDA develops when a person receives two expanded variants, one from each parent.
    • A person with one expanded variant is a carrier and can pass it to their children.
• Major Symptoms:
  • Movement problems: Symptoms usually begin between 5 and 15 years, causing unsteadiness and impaired coordination.
  • Speech and swallowing: Speech becomes slow and slurred, while swallowing becomes difficult.
  • Sensory problems: Hearing and vision deteriorate, and sensation is gradually lost.
  • Other effects: Fatigue occurs and the spine may curve to one side.
• Key Features:
  • Origin of expanded variants: Researchers found that 95% of the expanded variants came from just two long-normal variants.
    • These first became proto-mutations, then pre-mutations, and later developed into expanded variants.
  • Population pattern: FRDA has been reported mainly among people of European, North African, West Asian, and South Asian descent.
  • Consanguinity: Almost all cases diagnosed at Nizam’s Institute come from consanguineous marriages.
  • Genetic testing: Genetic tests can identify carriers and determine whether expanded variants were passed to children.
• Treatment: There is no cure for FRDA.