Complex hereditary spastic paraplegia associated with episodic visual loss caused by ACO2 variants

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Pathogenic variants in the ACO2 gene are primarily associated with infantile cerebellar-retinal degeneration.
• Recent studies have highlighted ACO2 variants presenting as complex hereditary spastic paraplegia (HSP) with diverse clinical manifestations.
• The phenotypic spectrum of ACO2-related disorders is still being elucidated.

Purpose of the Study:

• To report a novel case of complex hereditary spastic paraplegia (HSP) in a Japanese woman.
• To characterize the clinical presentation and genetic findings associated with compound heterozygous ACO2 variants.
• To identify a previously unrecognized phenotype of episodic visual loss in the context of febrile illness.

Main Methods:

• Clinical case report of a 20-year-old Japanese woman.
• Genetic analysis to identify causative variants in the ACO2 gene.
• Detailed neurological and ophthalmological examination.

Main Results:

• The patient presented with complex hereditary spastic paraplegia (HSP) due to compound heterozygous ACO2 variants.
• A new phenotype of episodic visual loss, specifically occurring during febrile illness, was observed.
• This expands the known clinical spectrum associated with ACO2 gene mutations.

Conclusions:

• Compound heterozygous ACO2 variants can manifest as complex hereditary spastic paraplegia (HSP).
• Episodic visual loss during febrile illness represents a novel phenotypic feature of ACO2-related disorders.
• Further research is warranted to understand the genotype-phenotype correlations and mechanisms underlying ACO2-associated neurological and visual symptoms.