To report a patient with hereditary spastic paraplegia type 80 (SPG80, UBAP1-related) and disabling generalized dystonia responsive to levodopa, and to outline diagnostic and therapeutic implications.

Hereditary spastic paraplegias are length-dependent corticospinal tract axonopathies that cause progressive spastic paraparesis. SPG80 results from truncating UBAP1 variants that disrupt ESCRT-I–mediated endosomal trafficking. Dystonia has been reported in several other HSP subtypes, although levodopa-responsive dystonia has not been described in association with a mixed HSP phenotype. Most patients with SPG80 exhibit no extrapyramidal features. This case expands the phenotypic spectrum of SPG80 by introducing dystonia as a potentially treatable manifestation. 

Patient presented at seven with gait issues, without significant birth or developmental history. Gait issues gradually progressed until he required a wheelchair. At thirty-seven, he started levodopa and showed 90% improvement in his gait function. On exam post-levodopa treatment, mentation is normal; he had no motor abnormalities of facial function, speech, or swallowing. He has signs of lower extremity spasticity, hyperreflexia, and positive Babinski signs bilaterally. Spastic gait was noted.  No dystonic postures were noted in the neck, trunk, upper or lower extremities, and there were no signs of Parkinson’s Disease. We conducted a retrospective chart review of this patient, including reviewing genetic testing. Nigrostriatal integrity was assessed with DAT-SPECT. 

This case expands the phenotypic spectrum of SPG80, demonstrating that UBAP1-related HSP can present as a mixed phenotype with corticospinal tract dysfunction (spastic paraparesis, not levodopa responsive) and a levodopa-responsive dystonia component. The combination of this clinical profile with a normal DAT-SPECT suggests a role for ESCRT-I–mediated endosomal trafficking in dopaminergic neurotransmission. Disruption of this pathway may influence D2 receptor signaling and lysosomal dynamics, providing insights into dopaminergic synaptic physiology. Management should be dual-targeted, combining dopaminergic therapy for the dystonic component with conventional spasticity-directed interventions for the HSP phenotype.