FA is a very rare, genetic, recessive disease, affecting 1/50,000 people. Originates from mutations in the “coding” of the mitochondria. Discovered by Nicholaus Friedreich in the early 1860’s. Both parents must have the dominant trait for a 25% chance of an offspring possessing the disease. Not necessarily a disease that kills you, but eventually a wheelchair and regular assistance will be required. Onset before age 20-25 year.

1. FRIEDREICH’S
ATAXIA
DONE BY : MUSTAFA KHALIL IBRAHIM
Tbilisi State Medical University
6th Year, 1st Semester, 1st Group
PEDIATRIC NEUROLOGY

2.  FA is a very rare, genetic, recessive disease,
affecting 1/50,000 people.
 Originates from mutations in the
“coding” of the mitochondria.
 Discovered by Nicholaus Friedreich in the early
1860’s.
 Both parents must have the dominant trait for a
25%chance of an offspring possessing thedisease.
 Not necessarily a disease that kills you, but
eventually a wheelchair and regular assistance
will be required.
 Onset before age 20-25 year.
Ataxia = A (lack of)
Taxia =(coordination)

3.  Mutations in the FXN gene cause Friedreich ataxia. This gene
provides instructions for making a protein called frataxin. Although its
role is not fully understood, frataxin is important for the normal
function of mitochondria,
 the energy-producing centers within cells. One region of the FXN
gene contains a segment of DNA known as a GAA trinucleotide
repeat.
 In people with Friedreich ataxia, the GAA segment is repeated 66 to
more than 1,000 times. The length of the GAA trinucleotide repeat
appears to be related to the age at which the symptoms of Friedreich
ataxia appear, how severe they are, and how quickly they progress.
People with GAA segments repeated fewer than 300 times tend to
have a later appearance of symptoms (after age 25) than those with
larger GAA trinucleotide repeats.

6.  Primary site of pathology is Spinal cord and
peripheral Nerves
 Degeneration of nerve tissue in the spinal cord,In particular
sensory nuerons essential(through connections with the
cerebellum) for directing muscle movement of the arms and legs
The spinal cord becomes thinner and nerve cells lose of their
myelin sheath.

7.  Vision and Hearing Impairment Weak Heart
 Scoliosis Slurred Speech
 No Motor Coordination
 Short Life Span (25-35 years)

8.  Mutations in the frataxin gene (located on chromosome 9) cause FA.
Frataxin, a protein, stores unneeded iron (releasing it only when
necessary) and controls the amount of iron in our mitochondria,
which require iron to produce ATP. Without frataxin, iron will float
freely in the mitochondria, and when too much iron is left in the
mitochondria, oxidative-stress (the buildup of harmful oxygen-based
free radicals) occurs. The oxidative-stress damages the mitochondria,
therefore, the ATP production drastically slows down. The absence of
frataxin destroys the nervous system (including the [peripheral]
nerves, sense of feeling, and spinal cord) and decreases the amount
of energy for the tissues and organs.

9. o Loss of coordination Muscle weakness.
o Spine curving (aggressive scoliosis).
o Vision impairment Slurred/slowed speech.
o Dysarthria.
o bladder dysfunction,
o spasticity particularly in the lower limbs.
o absent lower limb reflexes, and loss of position and
vibration sense
o Diabetes (about 20% of people with friedrich ataxia
develop carbohydrate intolerance and 10% of Diabetes
Mellitus).
o Heart disorder (Atrial Fibrillation, Cardiomyopathy,
Tachycardia).

10.  Typically, diagnosis begins with a basic physical exam and a
careful assessment of personal and family history.
 During the physical exam, the neurologist is likely to devote
special time and attention to testing reflexes, including the knee-
jerk reflex. Loss of reflexes occurs in most people with FA.
 Tests for frataxin mutations are highly reliable and can be used to
confirm or exclude a diagnosis of FA in almost all cases.

11.  Electromyography (EMG) is done by inserting a needlelike
electrode into a muscle and recording the electrical signals it
generates during contraction.
 A computerized tomography (CT scan) or magnetic resonance
imaging (MRI) might be performed to look for extensive changes
in the cerebellum, which are more common in spinocerebellar
ataxias than in FA.nerve conduction velocity test (NCV)
 Others
 ECG, EEG, ECHOGRAPHY.

14.  Vitamin e deficiency
 Paraneoplastic disorders
 Metabolic and immune disorders
 Multiple sclerosis

15.  DRUG THERAPY:
 idebenone:
 short chain quinine analogue act as potent
antioxidant and electron carrier
 Deferiprone
 Erythropoietin, pioglitazone.
 SUPPORTIVE THERAPY
Physiotherapy and mobility aids treatment
for cardiac failure.
Vitamin E .
 orthopedic surgery (scoliosis),Diabetics etc