Friedreich Ataxia - A short presentation

This is a presentation about the condition called Freidreich Ataxia, I have taken the content from renowned sources and the theme is from Slidesgo. I have also added a reference page to help you.

1. Freidreich Ataxia - Vaibhav Ramesh Babu Group 12

2. Introduction Friedreich ataxia (FA) is a rare, inherited disorder that causes progressive damage to the nervous system . This can cause movement and sensory symptoms and trouble with walking and gait. In FA, nerve fibers in the spinal cord and peripheral nerves break down, becoming thinner. In the brain, the cerebellum, part of the brain that coordinates balance and movement, is most affected. FA affects a person’s peripheral nerves, which carry information back and forth from the brain to the body using sensory and motor signals. This is why a person with FA develops motor weakness and sensory loss.

3. Friedreich's ataxia is an inherited condition caused by a defect in a gene called FXN, responsible for producing Frataxin. It is a recessive genetic disorder. This means you need to inherit a copy of the gene defect from both parents to develop it. Friedreich’s ataxia also often leads to: Speech, hearing and vision issues. Balance issues. Heart disease, especially hypertrophic cardiomyopathy. Scoliosis and/or foot deformities. Diabetes. This condition doesn’t affect thinking and reasoning abilities (cognitive functions).

4. Ethnic factors Who is at risk? FRDA affects Indo-European populations European. Middle Eastern. South Asian. North African. . It is rare in East Asians, sub-Saharan Africans, and Native Americans. A genetic mutation causes Friedreich’s ataxia. Anyone can inherit the condition if both of their biological parents carry a copy of the  FXN  gene mutation and pass that on to their child. Genetic factors

5. Symptoms - Classical Symptoms : - Neurological symptoms are universal, including dysarthria and loss of lower limb reflexes. - Over 90% present with ataxia. - Cardiac issues are prevalent, with symptoms such as heart enlargement, murmurs, and conduction defects. - Scoliosis occurs in about 60% of cases. - Some may develop diabetes, which worsens symptoms, especially in early onset cases.

6. - Other Symptoms : - Decreased visual acuity , potentially leading to blindness. - Hearing loss - Bladder and bowel symptoms are reported. - Advanced stages are marked by supraventricular tachyarrhythmias, primarily atrial fibrillation. - Cerebellar effects include nystagmus, dysmetria, and truncal ataxia. - Dorsal column involvement leads to loss of vibratory and proprioceptive sensation. - Disease Progression : - Progressive loss of coordination and muscle strength. - Mobility aids like canes, walkers, or wheelchairs are often needed by early 20s. - Increasing staggering gait and frequent falling. - By the third decade, full-time wheelchair use is required as standing and walking become impossible without assistance.

7. Pathophysiology The exact role of frataxin remains unclear. Without frataxin, the energy in the mitochondria falls, leading to further cell damage FRDA affects the nervous system, heart, pancreas, and other systems. Degeneration of nerve tissue in the spinal cord causes ataxia. The sensory neurons directing muscle movement of the arms and legs are particularly affected. The disease primarily affects the spinal cord and peripheral nerves and makes the spinal cord becomes thinner

8. Diagnosis Genetic testing can provide a conclusive diagnosis of FA. medical history and a thorough physical exam. difficulty with balance loss of sensation absence of reflexes and signs of other neurological problems Other tests include:

9. Diagnosis Electromyogram (EMG) Nerve conduction studies Electrocardiogram Echocardiogram Blood tests to check for the elevated glucose and vitamin E levels seen in FA MRI (magnetic resonance imaging) or CT (computed tomography) - thinning of spinal cord and cerebellum as well as to rule out other neurological conditions Progression of FA is measured using tools called FARS (Friedreich's Ataxia Rating Scale), mFARS (modified FARS) or SARA (Scale for Assessment and Rate of Ataxia) to measure neurological function and severity of a person’s symptoms over time.

10. Treatment There is currently no cure for FA. However, many of the symptoms and accompanying complications can be treated or managed to help people maintain function and daily activities as long as possible. Therapeutics : Omaveloxolone  received FDA approval under the brand name Skyclarys for the treatment of Friedreich's ataxia in February 2023. Approval in the EU is pending Rehabilitation : Physical therapy -intensive motor coordination, balance, and stabilization training to preserve gains. Speech therapy

11. Treatment Devices: Well-fitted orthoses Functional electrical stimulation or transcutaneous nerve stimulation Managing Cardiac Involvement:  ACE inhibitors such as enalapril, ramipril, lisinopril, or trandolapril Surgical Intervention: Titanium screws and rods inserted in the spine help prevent or slow the progression of scoliosis. Surgery to lengthen the Achilles tendon can improve independence and mobility to alleviate  equinus deformity.

12. - FRDA is characterized by progressive neurological and cardiac complications. - Life expectancy is often reduced compared to the general population. - Mobility declines over time, with many individuals requiring wheelchairs. - Cardiac issues are common and contribute to morbidity and mortality.. - Early diagnosis and proactive management are crucial for symptom alleviation. - Supportive care aims to slow disease progression and improve quality of life . - Ongoing research seeks to develop new treatments to address underlying causes. Prognosis

13. Case Patient Information: - Name: E.J - Age: 15 years old - Gender: Female - Date of Birth: May 5, 2009 - Ethnicity: Caucasian - Family History: Positive for Friedreich ataxia (FRDA) in older sibling (brother, aged 20). Presenting Complaint: Emily was referred to our pediatric neurology clinic due to concerns regarding gait abnormalities and frequent falls reported by her parents. They noticed these symptoms emerging gradually over the past year, accompanied by slurred speech and difficulty with fine motor tasks.

14. Medical History: Emily's developmental milestones were within normal limits. However, around age 14, she began experiencing progressive difficulties with balance and coordination. No significant medical history or traumatic events reported. Examination Findings: - Neurological Examination: - Gait ataxia with a wide-based stance and frequent stumbling. - Dysarthria noted with slurred speech. - Decreased deep tendon reflexes in lower limbs. - No sensory deficits or cranial nerve abnormalities detected. - Cardiac Examination: - Regular heart rhythm with no murmurs or abnormalities noted on auscultation. - ECG performed, showing normal sinus rhythm. - Other Systems: - Normal findings on ophthalmological and audiometric examinations. - No signs of scoliosis or significant musculoskeletal abnormalities observed.

15. Diagnostic Workup: - Genetic Testing: - Molecular genetic testing revealed homozygous GAA repeat expansions in the FXN gene, confirming the diagnosis of Friedreich ataxia. - Imaging: - MRI of the brain and spinal cord showed no structural abnormalities. - Cardiac Evaluation: - Echocardiography demonstrated normal cardiac structure and function with no evidence of hypertrophic cardiomyopathy. Management Plan: Emily's management plan focuses on multidisciplinary care involving neurology, cardiology, and rehabilitation services. - Symptomatic Treatment: - Physical therapy initiated to optimize mobility and prevent contractures. - Speech therapy for dysarthria management.

16. - Cardiac Monitoring: - Regular cardiac evaluations scheduled to monitor for the development of cardiac complications. - Genetic Counseling: - Genetic counseling provided to the family regarding inheritance patterns and recurrence risk for future pregnancies. Follow-Up: Emily will be followed up regularly to monitor disease progression and adjust management strategies accordingly. Referrals to other specialties, such as orthopedics or endocrinology, will be made as needed to address any emerging complications.

17. References https://en.wikipedia.org/wiki/Friedreich%27s_ataxia https://emedicine.medscape.com/article/1150420-overview?form=fpf https://www.ninds.nih.gov/health-information/disorders/friedreich-ataxia https://rarediseases.org/rare-diseases/friedreichs-ataxia/ https://medlineplus.gov/genetics/condition/friedreich-ataxia/ https://www.ncbi.nlm.nih.gov/books/NBK563199/ https://www.orpha.net/en/disease/detail/95 https://www.hopkinsmedicine.org/health/conditions-and-diseases/friedreich-ataxia#:~:text=Friedreich's%20ataxia%20is%20an%20inherited%20disorder%20that%20affects%20some%20of,to%20get%20worse%20over%20time .

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