Friedreich Ataxia: Multidisciplinary Clinical Care

Abstract

Friedreich ataxia (FRDA) is a multisystem disorder affecting 1 in 50,000–100,000 person in the United States. Traditionally viewed as a neurodegenerative disease, FRDA patients also develop cardiomyopathy, scoliosis, diabetes and other manifestation. Although it usually presents in childhood, it continues throughout life, thus requiring expertise from both pediatric and adult subspecialist in order to provide optimal management. The phenotype of FRDA is unique, giving rise to specific loss of neuronal pathways, a unique form of cardiomyopathy with early hypertrophy and later fibrosis, and diabetes incorporating components of both type I and type II disease. Vision loss, hearing loss, urinary dysfunction and depression also occur in FRDA. Many agents are reaching Phase III trials; if successful, these will provide a variety of new treatments for FRDA that will require many specialists who are not familiar with FRDA to provide clinical therapy. This review provides a summary of the diverse manifestation of FRDA, existing symptomatic therapies, and approaches for integrative care for future therapy in FRDA.

Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich’s ataxia

“…Ceramides are believed to be a main factor in reorganizing microscopic membrane rafts into signaling platforms in response to stress. ( 39 ) Ceramides can induce apoptosis, increasing the risk for type 2 diabetes and cardiovascular disease, which fits with an involvement in the FRDA disease etiology ( 1 ). Combining results from the lipid profiling and isotope tracing experiments, our data from fibroblast cells indicate that frataxin deficiency enhances ceramide biosynthesis, contributing to the ceramide accumulation in the FRDA fibroblasts, while hydrolysis of more complex sphingolipids (Hex1Cer and SM) does not contribute to the ceramide accumulation ( Fig.…”

“…Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with an incidence of 1 in 29,000 (1). Currently it has no approved treatment (1).…”

“…Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with an incidence of 1 in 29,000 (1). Currently it has no approved treatment (1). The main clinical features in FRDA include gait and limb ataxia, dysarthria, sensory loss, and cardiomyopathy (2).…”

Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich’s Ataxia

“…Patients display signs of cerebellar, limb and sensory ataxia with symptoms onset generally during the first two decades of life ( Cook and Giunti, 2017 ; Smith and Kosman, 2020 ). Diabetes, blindness and deafness are additional phenotypes that appear in the course of the disease but with a different incidence frequency, onset and progression ( Parkinson et al, 2013 ; Lynch et al, 2021 ).…”

Emerging Therapies in Friedreich's Ataxia: A Review

“…ataxia, upper motor neuron spasms, spasticity, contractures, weakness, fatigue, neuropathic or orthopaedic pain, restless legs, sleep disturbance, aids to mobility and fall prevention, dysarthria, dysphagia, vision loss, hearing loss, bladder or bowel dysfunction, sexual dysfunction, cardiac arrhythmias and heart failure, scoliosis and foot deformities, diabetes and mental health issues) are most effectively managed in a multidisciplinary setting, with rehabilitation medicine and with medications available for such symptoms in other, more common diseases. 44 With better cardiac care, [45][46][47] patients with FRDA are living longer and consequently experiencing significant disabilities related to chronic neurological decline. While the early stages of the disease primarily involve loss of ambulation 48 and the need for accommodations at school or work, 49 later stages bring an increasing need for assistance with activities of daily living, complications of being bedbound (e.g.…”