From the Guidelines
Friedreich ataxia can present as late as the sixth decade of life, with late-onset and very late-onset forms occurring after age 25 and 40, respectively. The age of onset for Friedreich ataxia is typically between 5 to 15 years, as stated in the study by 1. However, the severity of phenotypic features of FA is variable, and later onset also occurs. Key factors influencing the age of onset include the size of the GAA repeat expansion in the FXN gene, with smaller expansions associated with later onset and milder symptoms. Some notable points about Friedreich ataxia include:
- The normal size for the GAA repeat is ≤30 copies, and affected individuals typically have >70 triplets on each copy of this gene, as noted in 1
- An intermediate size (30–70) is classified as premutation, which is more susceptible to expansion in future generations
- Cardiac disease is the most life-threatening manifestation of FA, and additional systemic features include progressive cerebellar dysfunction, ataxia, scoliosis, diabetes mellitus, impaired speech, and loss of vision and hearing
- The spectrum of phenotypic features of FA fits best with a mitochondrial disorder, although frataxin is encoded by nuclear DNA, as discussed in 1. Given the variability in age of onset and disease severity, it is essential to consider the individual patient's characteristics and genetic mutation when assessing the likelihood of late-onset Friedreich ataxia.
From the Research
Latest Presentation of Friedreich Ataxia
The latest Friedreich ataxia can present is in the very-late-onset form, which occurs after the age of 40 years 2.
Characteristics of Very-Late-Onset Friedreich Ataxia
Very-late-onset Friedreich ataxia may not show characteristic features of the disorder, such as:
- Areflexia
- Dysarthria
- Sensory neuropathy
- Extensor plantars
- Amyotrophy
- Cardiac involvement
- Diabetes mellitus
- Scoliosis Additionally, atypical features such as spasticity, brisk reflexes, and laryngeal dystonia may be present 2.
Comparison with Other Forms of Friedreich Ataxia
In contrast to the classical form of Friedreich ataxia, which typically presents in the first or second decade, very-late-onset Friedreich ataxia is a rare form of the disease 2. The classical form is characterized by unsteadiness in standing and walking, slowly progressing to wheelchair dependency usually in the late teens or early twenties 3, 4.