Paulo Sgobbi, Igor Braga Farias, Paulo de Lima Serrano, Bruno de Mattos Lombardi Badia, Hélvia Bertoldo de Oliveira, Alana Strucker Barbosa, Camila Alves Pereira, Vanessa de Freitas Moreira, Marco Antônio Troccoli Chieia, Adriel Rêgo Barbosa, Pedro Henrique Almeida Fraiman, Vinícius Lopes Braga, Roberta Ismael Lacerda Machado, Sophia Luiz Calegaretti, Isabela Danziato Fernandes, Roberta Correa Ribeiro, Marco Antonio Orsini Neves, Wladimir Bocca Vieira de Rezende Pinto, and Acary Souza Bulle Oliveira
An 18-year-old man presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated with painless strabismus, intellectual disability, urinary incontinence, bilateral progressive visual loss, and cognitive decline since early adolescence. A neurological examination disclosed spastic dysarthria, left eye divergent strabismus, bilateral ophthalmoparesis, impaired smooth pursuit, severe spastic paraparesis of the lower limbs with global brisk tendon reflexes, bilateral extensor plantar responses, and bilateral ankle clonus reflex. Bilateral dysdiadochokinesia of the upper limbs, Stewart-Holmes rebound phenomenon, bilateral dysmetria, and a bilateral abnormal finger-to-nose test were observed. Markedly reduced bilateral visual acuity (right side 20/150, left side 20/400) and moderate to severe optic atrophy were detected. Neuroimaging studies showed cerebellar atrophy and bilateral optic nerves and optic tract atrophy as the main findings. As a complicated Hereditary Spastic Paraplegia, autosomal dominant Spinocerebellar Ataxia, or inherited neurometabolic disorders were suspected, a large next-generation sequencing-based gene panel testing disclosed the heterozygous pathogenic variant c.162-1G>A in intron 1 of the PNPT1 gene. A diagnosis of PNPT1-related spastic ataxia was established. Clinicians must be aware of the possibility of PNPT1 pathogenic variants in cases of spastic ataxia and spastic paraplegias that are associated with optic atrophy and marked cognitive decline, regardless of the established family history of neurological compromise.