2025 American Academy of Neurology Abstract Website

Objective:

To describe a case of dystonia and ataxia in a patient with ubiquitin-like modifier activating enzyme 5 gene (UBA5) and calcium voltage-gated channel subunit alpha1 A (CACNA1A) genetic mutations.

Background:

CACNA1A mutations are known to cause spinocerebellar ataxia type 6 (SCA6) which typically presents with adult-onset, slowly progressive ataxia. Although UBA5 mutations are typically known to cause early infantile epileptic encephalopathy-44, they can more rarely cause cerebellar ataxia. Symptoms such as dystonia are rare in both UBA5 and CACNA1A mutations.

Design/Methods:

A 56-year-old female presented with isolated cervical dystonia in 2013 and was symptomatically managed with botulinum toxin injections for several years. Her dystonia progressed to her arms and she also developed ataxia requiring the use of a walker. By 2023, the patient required a wheelchair and a feeding tube. Neurologic examination demonstrated cervical dystonia with head tilt to the left and rotation to the right, dystonic posturing of the bilateral hands, ataxia on finger-to-nose testing, and severe scanning, dysarthric speech. Notable family history includes a brother who suffered from childhood-onset ataxia, cervical dystonia, and behavioral issues including aggressive outbursts.

Results:

MRI revealed cerebellar atrophy. Genetic testing revealed a heterozygous autosomal recessive variant c.1111 G>A p.(A371T) of gene UBA5 and a homozygous autosomal dominant variant c.3538 A>C p.(N1180H) of gene CACNA1A, with 22 CAG repeats.

Conclusions:

This case illustrates several important points: (1) Despite involving a homozygous CACNA1A mutation with 100% known penetrance, there was no parental history of symptoms; (2) Although CACNA1A/UBA5-related diseases are known to cause cerebellar ataxia, this patient presented with several years of dystonia before the ataxia developed, which delayed diagnosis; (3) It is unclear how/if CACNA1A/UBA5 mutations interact and whether this affects the phenotypic presentation; (4) The coexistence of adult-onset dystonia and ataxia should prompt investigation for CACNA1A/UBA5 mutations so that appropriate counseling can occur.