Pearls & Oy-sters: Hereditary Spastic Paraplegia Type 15 Presenting as Juvenile Onset Levodopa-Responsive...

We report the case of a 27-year-old man with a history of speech delay and chronic, progressive movement disorder. He first developed gait difficulty at the age of 12. Given clinical signs of bradykinesia and resting tremor, he received a clinical diagnosis of childhood-onset parkinsonism. Treatment with oral levodopa initially improved symptoms, but after 2 years, he developed motor fluctuations and dyskinesias. Additional signs of spasticity and brain MRI showing a thin corpus callosum prompted genetic testing that identified a heterozygous pathogenic variant in the PRKN gene. However, he exhibited a progressive loss of response to chronic dopaminergic therapy, first with oral and later with continuous levodopa-carbidopa intestinal gel infusion, with disease progression over 7 years. This progression led to further genetic testing and the diagnosis of hereditary spastic paraplegia type 15 (SPG 15). Advancing motor symptoms prompted deep brain stimulation and botulinum toxin injections, although these had limited benefit. This case highlights the challenges of diagnosing and managing juvenile-onset parkinsonism and the value of comprehensive genetic analysis in evaluating genotypic-phenotypic correlations. Hereditary spastic paraplegias (HSPs) are a rare group of neurodegenerative disorders with diverse clinical and genetic features. They can be inherited in autosomal dominant, recessive, X-linked, or mitochondrial patterns. The SPG15 subtype (or HSP-ZFYVE26), caused by pathogenic variants in the ZFYVE26 gene, is a common form of autosomal recessive HSP. Presenting symptoms vary but commonly include cognitive impairment with a history of speech delay or learning disability and balance impairment or clumsiness from spasticity of the lower limbs.