From the Guidelines
Friedreich ataxia symptoms typically include progressive difficulty with coordination and balance, which usually begins in childhood or adolescence, and can lead to severe morbidity and mortality due to cardiac complications, such as hypertrophic cardiomyopathy and arrhythmias, which are the most frequent cause of death in FA 1. The disease affects the spinal cord, peripheral nerves, and cerebellum, causing unsteady gait, clumsiness, and slurred speech. Muscle weakness, particularly in the legs, develops over time, often leading to wheelchair dependency within 10-15 years of symptom onset. Many patients develop scoliosis (curvature of the spine) and foot deformities like high arches or clubfoot. Other symptoms include:
- Vision and hearing impairments
- Diabetes mellitus
- Difficulty swallowing
- Speech becomes increasingly difficult to understand as the disease progresses These symptoms result from the genetic mutation in the FXN gene, which reduces production of frataxin protein, leading to mitochondrial dysfunction and damage to nerve and muscle cells. The disease is progressive, with symptoms typically worsening over time, though the rate of progression varies between individuals. According to the American Heart Association, cardiac manifestations consist of LV hypertrophy with fibrosis and scarring, arrhythmias, and progressive HF, which are the most life-threatening aspects of the disease 1.
The severity of most phenotypic features of FA is variable, and the age of onset can range from 5 to 15 years, although later onset also occurs 1. The size of the expanded GAA repeats correlates loosely with the manifestations of the disease, and other genetic and environmental factors can influence the age of onset and progression of disease 1. Therefore, early diagnosis and management of cardiac involvement are crucial to improve morbidity, mortality, and quality of life in patients with Friedreich ataxia 1.
From the Research
Friedrietch Ataxia Symptoms
- Friedreich ataxia (FA) is a multisystem disorder that affects 1 in 50,000-100,000 people in the United States 2
- The phenotype of FA 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 2
- Vision loss, hearing loss, urinary dysfunction, and depression also occur in FA 2
- Speech and language disorders are prominent signs in FA, which significantly impact on patients' quality of life 3
- FA patients often present dysarthria, resulting from central and peripheral causes and additional primary language disorders 3
- Speech disturbances have peculiar characteristics, although variable among patients, and progress along the disease course 3
Common Symptoms
- Dysarthria, a collective term referring to a group of movement disorders affecting the muscular control of speech 4
- Cardiomyopathy, scoliosis, diabetes, and other manifestations 2
- Vision loss, hearing loss, urinary dysfunction, and depression 2
- Speech and language disorders, including dysarthria and primary language disorders 3
Treatment and Management
- Management of FA is currently focused on symptomatic management, delivered by a multidisciplinary team 5
- There is insufficient and low or very low quality evidence from either RCTs or observational studies to determine the effectiveness of any treatment for speech disorder in FA 4
- Tailored speech training or non-invasive neuromodulation appear as the most reliable therapeutic options to be validated in future trials 3
- Phase II clinical trials in agents that address the aberrant silencing of the frataxin gene need to be translated into large placebo-controlled Phase III trials to help establish their therapeutic potential 5