Friedreich’s Ataxia

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 T bilisi S tate M edical U niversity 6 th Year, 1 st Semester, 1 st 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 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. DEFINITION 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. GENETICS

4. 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. PATHOLOGY

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

6. 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 . ETIOLOGY

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

8. 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. DIAGNOSIS

9. Electromyography (EMG) is done by inserting a needlelike electrode into a muscle and recording the electrical signals it generates during contraction. A co mputerized 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.

10. Vitamin e deficiency Paraneoplastic disorders Metabolic and immune disorders Multiple sclerosis DIFFERENTIAL DIAGNOSIS

11. 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 TREATMENT