A Case of Late-Onset Hereditary Spastic Paraplegia (HSP)

Overview:Hereditary spastic paraplegia (HSP) represents a heterogeneous group of genetic disorders of the nervous system, which is identified by “progressive lower-limb” spasticity and weakness. Autosomal dominant HSP due to ATL1 (SPG3A) mutations typically presents in childhood, while late-onset cases remain exceedingly rare and often difficult to diagnose due to overlap with acquired spastic paraparesis and age-related neurological conditions. Case Presentation:We report about a 61 year old male with progressively worsening gait difficulty and lower-limb stiffness. Although he recalled mild walking difficulty since childhood, rapid worsening over one year prompted evaluation. Neurological examination revealed lower-limb spasticity, clonus, hyperreflexia and bilateral extensor plantar responses without sensory, cerebellar, cognitive, or bladder involvement. Significant autosomal dominant family history was noted, with two affected siblings. Investigations & Diagnosis:Routine metabolic, nutritional, autoimmune, and infectious profiles were normal. Electrophysiology demonstrated intact peripheral nerve function. MRI spine showed advanced multilevel degenerative disk and facet changes, while MRI brain demonstrated frontal periventricular hyperintensities suggestive of the “ears of the lynx” sign. Whole-exome approaches pointed out a likely pathogenic ATL1 missense version (c.1376A>G; p.Tyr459Cys), confirming late-onset ATL1-HSP. Differential diagnoses including primary lateral sclerosis, spinocerebellar ataxia, and chronic myelopathy were excluded. Management & Outcome:The patient received oral baclofen and structured physiotherapy. At six-month follow-up, gait stability and spasticity demonstrated modest improvement, with stable upper-limb strength and no new neurological deficits. Conclusion:This case highlights an uncommon late-onset presentation of ATL1-associated HSP, emphasizing the need to consider genetic etiologies in adult-onset spastic paraparesis, particularly with subtle lifelong symptoms and positive family history. Genetic testing remains essential for timely diagnosis, counseling, and management.