ACO2 and Spastic paraplegia: Other homozygous or compound heterozygous ACO2 mutations causing about 50% of normal enzyme activity have been linked to a spectrum of phenotypes, including complex spastic paraplegia complicated by intellectual disability and microcephaly (Bouwkamp et al., 2018), complex spastic paraplegia with episodic visual loss (Tozawa et al., 2021), and recessive optic atrophy with or without spastic paraplegia (Marelli et al., 2018; Gibson et al., 2020).