Clinical features and genotype in COQ4 associated hereditary spastic paraplegia: a case report and a literature reanalysis

COQ4 mutation often leads to a fatal multi-system disease in infants. Recently, it was reported that the biallelic COQ4 variants may be a potential cause of hereditary spastic paraplegia (HSP). This study aims to describe the clinical features and genotype of the COQ4 associated hereditary spastic paraplegia (HSP).

We reported a case of HSP with COQ4 variants, and a literature reanalysis was performed.

Three studies with a total of 1309 patients with HSP of unknown cause were included, and 13 (1%) patients were found to have biallelic COQ4 variants. Seven patients fulfilled pure HSP, and six patients fulfilled complicated HSP. The median age of these patients was 24 years (range 15 to 65 years), and the median year of disease onset was 14 years (range 1 to 55 years). The most common clinical manifestations were lower limb spasticity (100%), hyperreflexia (100%), Babinski sign (77%), reduced muscle strength (53.8%) cerebellar ataxia (23.1%), seizures (23.1%) and dysarthria (23.1%). Including our case, 16 different variants located in exon 2, exon 4, exon 5, exon 6, exon 7 and two introns of the COQ4 gene have been identified in patients with HSP. All started CoQ10 supplementation, but follow-up was reported in only one patient.

COQ4 variants were associated with childhood, adolescent, and adult onset HSP, which has a relatively mild course. The efficiency of CoQ10 supplement in patients with COQ4 associated HSP need to be classified in the future study.