Three Adult-Onset Autosomal Recessive Ataxias: What Adult Neurologists Need to Know

Abstract

Purpose of review: In this review we seek to raise awareness of 3 autosomal recessive ataxias that look different clinically when presenting in adulthood rather than childhood.

Recent findings: A study found a high allelic frequency for repeat expansions in the RFC1 gene, a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, which presents exclusively in adults. This implies that autosomal recessive etiologies of adult-onset cerebellar ataxias may be more common than previously thought.

Summary: Adult-onset cerebellar ataxias are commonly caused by mutations inherited in either an autosomal dominant or X-linked pattern, as most autosomal recessive mutations cause disease at earlier ages. However, some autosomal recessive etiologies such as late-onset Tay-Sachs disease, very late-onset Friedreich ataxia, and autosomal recessive spastic ataxia of Charlevoix-Saguenay emerge in adulthood, with age at presentation influencing the progression and clinical signs of the disease. This review will cover the genetics, clinical presentation, and necessary diagnostic steps required to identify 3 causes of autosomal recessive cerebellar ataxia that manifest differently in adults vs children.

Figure 1. Characteristic MRI Findings in a Patient With Late-Onset Friedreich Ataxia

Increased size of the sulci between the folia of the cerebellum and increased size of the 4th ventricle. Case courtesy of Dr Chris O'Donnell, Radiopaedia.org, rID: 19772.

Figure 2. Characteristic MRI Findings in a Patient With Autosomal Recessive Spastic Ataxia of Charlevoix–Saguenay

Atrophy of the superior cerebellar vermis with thinning of the corpus callosum. Case courtesy of Dr. Maxime St-Amant, Radiopaedia.org, rID: 18854.