PNPT1 Spectrum Disorders: An Underrecognized and Complex Group of Neurometabolic Disorders

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Spastic ataxia and spastic paraplegia are complex neurological disorders.
• Optic atrophy and cognitive decline can be associated features.
• Genetic etiologies are diverse, including hereditary spastic paraplegia and spinocerebellar ataxias.

Observation:

• An 18-year-old male presented with infancy-onset spasticity, cerebellar ataxia, strabismus, intellectual disability, and progressive visual loss.
• Neurological examination revealed spastic dysarthria, ophthalmoparesis, spastic paraparesis, and cerebellar signs.
• Ophthalmological assessment showed reduced visual acuity and optic atrophy.

Findings:

• Neuroimaging demonstrated cerebellar and optic nerve/tract atrophy.
• Next-generation sequencing identified a pathogenic variant (c.162-1G>A) in the PNPT1 gene.
• A diagnosis of PNPT1-related spastic ataxia was established.

Implications:

• PNPT1 variants should be considered in spastic ataxia/paraplegia with optic atrophy and cognitive decline.
• This finding expands the spectrum of PNPT1-related neurological disorders.
• Awareness of PNPT1 variants is crucial for accurate diagnosis, even without a family history.