To highlight VLOFA as a cause of the late life phenotype of hereditary spastic paraplegia.

Friedreich’s Ataxia (FA) is an autosomal recessive hereditary ataxia due to GAA trinucleotide repeat expansion, or rarely point mutation, in intron 1 of X25 gene on chromosome 9q13-21.1. Clinical presentations of Late-onset FA (LOFA; onset 25-39 years) and VLOFA (onset ≥ 40 years) are distinct from young onset FA, which can hamper prompt and accurate diagnosis.

Two sisters, S-1 age 63y and S-2 age 67y presented with worsening gait, incoordination, and speech changes, S-1 over 1 year, S-2 over 8 years. There was no parental consanguinity. Neurological examination revealed bilateral lower extremity spasticity with diffuse hyper-reflexia, spastic dysarthria, distal vibratory deficits, and saccadic oculomotor pursuit. Cerebellar motor examination demonstrated end-point dysmetria in the upper extremities and jerking-in-plane with superimposed lateral movements on heel-to-shin testing. Gait was spastic with irregular cadence and widened stance, tandem gait was impossible, and Romberg test was positive. Plantar responses were normal in S-1, equivocal in S-2.

Normal studies included MRI brain and spinal cord, sensory-motor nerve conduction studies in arms and legs, and evaluation for peripheral neuropathies. Hereditary spastic paraplegia gene panel in S-2 was normal. Hypothesis-driven targeted genetic testing in S-1 demonstrated homoallelic pathogenic expanded allele (> 75 GAA trinucleotide repeats) in the frataxin gene, confirming the diagnosis of VLOFA. Subsequent testing in S-2 revealed GAA allelic expansions of 1066 and 99.

VLOFA may present with the phenotype of hereditary spastic paraplegia with superimposed features of cerebellar ataxia.  Shorter numbers of trinucleotide repeats (< 400 in LOFA vs > 600-1000s in FA) inversely correlate with disease onset, progression and severity. Detailed neurological examination and high degree of suspicion for LOFA / VLOFA are important when evaluating adult patients with evolving spasticity with or without ataxia.