A COA8 homozygous mutation presenting as an intermediate CMT with leukopathy

Patients with cytochrome c oxidase (COX) deficiency exhibit clinical heterogeneity, with onset ranging from infancy to adulthood. COA8-related disorders typically present in childhood with acute symptoms and cavitating posterior leukoencephalopathy, though milder, muscle-predominant forms have recently been reported. We describe a 54-year-old woman with a neuropathy with slow conduction velocities and leukoencephalopathy, associated with hearing loss and migraine. Neurological examination showed mildly high-arched feet, mild dysmetria without lateralization, and distal hypoesthesia. There was no gastro-intestinal involvement. Targeted NGS for hereditary neuropathies was unremarkable. The neurometabolic workup was negative. Whole genome sequencing identified a homozygous COA8 mutation (c.476 + 1G > A), confirmed by muscle biopsy showing COX deficiency and significantly reduced complex IV activity. This case expands the phenotypic spectrum of COA8-related diseases and suggests that a mitochondrial etiology should be considered in cases of neuropathy with intermediate conduction velocities associated with leukoencephalopathy, even with late onset.