What is the management plan for a patient with Friedreich's ataxia?

Management of Friedreich's Ataxia

Friedreich's ataxia requires aggressive multidisciplinary management centered on respiratory care, cardiac monitoring, and nutritional support, with omaveloxolone (Skyclarys) being the only FDA-approved disease-modifying therapy available.

Disease-Modifying Pharmacotherapy

• Omaveloxolone (Skyclarys) is the only FDA-approved medication for Friedreich's ataxia, functioning as an Nrf2 activator that addresses mitochondrial dysfunction, though it is not curative 1.
• Antioxidant therapies including idebenone and coenzyme Q10 with vitamin E have shown no significant neurological benefit in randomized trials, with low-quality evidence neither supporting nor refuting their use 2.
• Gene therapy, protein replacement, and epigenetic approaches represent the most promising future prospects for enduring disease modification by addressing the underlying frataxin deficiency 1.

Respiratory Management

Respiratory complications are a leading cause of premature death and require proactive monitoring starting early in the disease course.

Monitoring and Assessment

• Conduct respiratory assessments at least twice yearly to track lung function decline, with forced vital capacity (FVC) and peak cough flow rate as primary measurements 3.
• Perform overnight polysomnography in adolescents with Friedreich's ataxia, particularly those with suspected sleep-disordered breathing or progressive lung function decline 3.

Therapeutic Interventions

• Implement respiratory muscle strength training (RMST) to improve ventilatory pattern, lung volumes, respiratory muscle strength, and quality of life 3.
• Use cough assist devices to improve FVC, peak cough flow, and mid-expiratory flows in patients with inefficient cough 3.
• Consider nebulized hypertonic saline or inhaled mannitol as adjuncts to airway clearance 3.
• For progressive diffuse lung disease unresponsive to aggressive therapy, consider non-infectious causes including interstitial lung disease and initiate early corticosteroid treatment 3.

Cardiac Management

Cardiac disease is the most life-threatening manifestation and the most frequent cause of death in Friedreich's ataxia, requiring vigilant monitoring.

Screening and Monitoring

• Perform regular cardiac screening with ECG and echocardiography as cardiac involvement may be asymptomatic but is common 3, 4.
• Maintain a low threshold for investigating symptoms or ECG findings, as progression of conduction abnormalities may be unpredictable 3.
• Recognize that patients are at risk for sudden cardiac death even with only mildly decreased left ventricular function 3.

Cardiac Interventions

• Implement standard heart failure therapies for patients with cardiomyopathy according to established guidelines 3.
• Place ICD for secondary prevention in patients who survive ventricular fibrillation or hemodynamically unstable ventricular tachycardia with LVEF ≤40% 3, 4.
• Consider primary prevention ICD following standard guidelines for dilated cardiomyopathies 3.

Nutritional Management

Malnutrition is a significant comorbidity requiring early and aggressive intervention.

• Assess adequacy and safety of nutritional intake at least annually 3.
• Provide supplemental calories by oral or enteral route for patients with worsening nutritional status 3.
• Consider early gastrostomy insertion in patients with unsafe swallow or inadequate nutritional intake 3.
• Place gastrostomy when patients present with progressive nutritional insufficiency, respiratory deterioration, and aspiration secondary to dysphagia unresponsive to conservative measures 3.

Physical and Occupational Therapy

• Initiate early and continued physiotherapy to mitigate contractures and scoliosis, with regular exercise advised to maintain function even in younger mobile children 3.
• Continue regular exercise programs throughout the disease course to preserve functional capacity 3.

Multidisciplinary Care Coordination

• Establish multidisciplinary "one-stop" service provision involving neurology, cardiology, pulmonology, nutrition, physical therapy, and genetics subspecialties 3.
• Provide genetic counseling for families, as genetic testing confirms diagnosis and identifies at-risk family members 3.
• Screen regularly for and treat diabetes mellitus, which commonly develops in Friedreich's ataxia 3.

Critical Pitfalls to Avoid

• Do not delay gastrostomy placement in patients with progressive dysphagia, as this increases aspiration risk and respiratory complications 3.
• Avoid neglecting regular respiratory assessments, which leads to missed opportunities for early intervention before irreversible decline 3.
• Do not underestimate cardiac risk in patients with mild left ventricular dysfunction, as sudden cardiac death can occur 3.
• Ensure coordination across all subspecialties rather than fragmented care, which is essential for comprehensive management of this multisystem disorder 3.