What is Spinocerebellar Ataxia (SCA) type 5?

Spinocerebellar Ataxia Type 5 (SCA-5)

Spinocerebellar ataxia type 5 (SCA-5) is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar atrophy, primarily affecting balance, coordination, and speech. 1

Clinical Features

• SCA-5 is typically characterized by slowly progressive adult-onset ataxia, though rare infantile presentations have been documented 2
• Primary symptoms include loss of balance, coordination difficulties, and slurred speech (dysarthria) 1
• In contrast to other SCAs, SCA-5 often presents with relatively pure cerebellar ataxia with less involvement of other neurological systems 1, 3
• Rare infantile-onset cases may present with ataxic cerebral palsy and developmental delay as early as 6 months of age 2

Genetics and Pathophysiology

• SCA-5 is caused by mutations in the SPTBN2 gene, which encodes β-III spectrin, a protein important for maintaining Purkinje cell structure and function 1
• Unlike many other SCAs that are caused by trinucleotide repeat expansions, SCA-5 is classified as a non-repeat mutation SCA 1
• The disease mechanism involves dysfunction of Purkinje neurons in the cerebellum, leading to cerebellar atrophy 1

Diagnosis

• Diagnosis relies on a combination of clinical neurological examination, neuroimaging, and confirmatory genetic testing 4
• MRI of the head without contrast is the preferred initial imaging modality, which typically shows cerebellar atrophy 4
• Genetic testing for mutations in the SPTBN2 gene confirms the diagnosis 2, 1
• Early in the disease, conventional neuroimaging may be unremarkable, making genetic testing crucial 4

Imaging Findings

• MRI typically reveals cerebellar atrophy, particularly affecting the vermis and cerebellar hemispheres 4
• Advanced MRI techniques such as diffusion-weighted imaging and diffusion tensor imaging may detect early changes before conventional MRI shows abnormalities 4
• CT imaging is less sensitive than MRI for evaluating cerebellar atrophy but may be useful in identifying calcifications in some rare SCA subtypes 4

Treatment and Management

• Currently, there is no disease-modifying treatment to slow or halt the progression of SCA-5 1, 5
• Clinical care focuses on managing symptoms through:
  • Physical therapy to maintain balance and coordination 1
  • Occupational therapy to assist with activities of daily living 1
  • Speech therapy to address dysarthria 1
• Symptomatic medications may be used off-label, though no FDA-approved drugs specifically for SCA exist 5

Prognosis

• SCA-5 is generally considered to have a more benign course compared to other SCAs, with slower progression and less systemic involvement 1, 3
• Life expectancy is typically not significantly reduced, unlike some other forms of SCA 1
• The disease is progressive, with gradual worsening of ataxia and other cerebellar symptoms over time 1

Research Directions

• Emerging therapeutic approaches include antisense oligonucleotides and RNA-based therapies 6
• Research into the pathobiology of SCAs has identified potential therapeutic targets, though development is challenged by the heterogeneity of these disorders 1