Spinocerebellar ataxia type 25 presenting with peripheral neuropathy: a case report

Abstract

Case Presentation: A 2.5-year-old female presented with progressive gait impairment, characterized by disequilibrium and lower limb rigidity, associated with upper limb intention tremor. At the age of 4, magnetic resonance revealed diffuse cerebellar atrophy. By age 10, the patient was diagnosed with obstructive sleep apnea and excessive daytime somnolence, with nocturnal sleep disturbances including coughing and choking. In school, she experienced learning difficulties across all subjects and exhibited age-inappropriate behavior. She achieved literacy at age 9. Upon neurological examination, the patient presented with hyporeflexia, ataxic gait, apallesthesia, and loss of proprioception in the lower limbs, along with muscle hypotonia and dysmetria in all four limbs. Orthopedic findings included thoracic scoliosis and pes cavus. Electroneuromyography showed axonal peripheral polyneuropathy. To further investigate, she underwent whole exome sequencing, which revealed a heterozygous likely pathogenic variant in the PNPT1 gene. The patient was then diagnosed with Spinocerebellar Ataxia type 25, due to compatible clinical presentation and genetic findings. Discussion: Spinocerebellar Ataxias are a heterogeneous group of autosomal dominant neurodegenerative disorders. Variable age of onset is observed among Spinocerebellar Ataxia subtypes. Spinocerebellar Ataxia type 25 is an autosomal dominant disorder caused by mutations in the gene encoding polyribonucleotide nucleotidyltransferase 1 (PNPase 1; PNPT1), located in the Spinocerebellar Ataxia type 25 linkage interval. Symptoms described in the literature include progressive ataxia, Cerebellar atrophy, and sensory neuropathy. Some patients exhibit gastrointestinal disorders, such as vomiting and abdominal pain. Scoliosis and urinary problems have also been observed. It is paramount to underscore that Spinocerebellar Ataxia type 25 exhibits phenotypic variability and incomplete penetrance. The clinical presentation can become evident within the first year of life and can vary from prominent sensory neuropathy with minimal cerebellar ataxia to prominent cerebellar ataxia with minimal sensory neuropathy. Final Comments: This report highlights the diagnostic challenge of an extremely rare pathology, with a prevalence of less than one per million people worldwide, and only two other cases described in Brazil. Cerebellar signs and sensory neuropathy must draw the clinician's attention to this diagnosis. Due to its autosomal dominant nature, it is paramount to screen for these signs—even if mild—in first-degree relatives. In this report, we describe a case of Spinocerebellar Ataxia type 25, marking one of Brazil's earliest clinical documentations of this rare genetic condition.