Coenzyme Q4 gene compound heterozygous mutations cause hereditary spastic paraplegias: a case report.

backgroundComplicated hereditary spastic paraplegias (complicated HSPs) are a subtype of hereditary spastic paraplegias (HSPs), which refer to a group of hereditary neurodegenerative diseases of the nervous system characterized by stiffness of the lower limbs and hyperreflexia, and are accompanied by other symptoms. HSPs exhibit high clinical and genetic heterogeneity, making diagnosis challenging, especially in early-onset cases. Mutations in the COQ4 gene have been rarely reported to be associated with complicated HSPs, and most previously reported COQ4-related HSP cases lack detailed clinical descriptions or involve novel mutations. Through this case report, we aim to expand the genotype spectrum of complicated HSPs caused by COQ4 gene variants, provide detailed clinical and genetic data for early-onset HSP, and help improve the understanding and diagnosis of COQ4-related neurodegenerative diseases in clinical practice. CASE PRESENTATION: A 12-year-and-9-month-old Chinese boy presenting with progressive spastic paraplegia of both lower limbs, gait disturbance, and mild tremor who had an undetermined genotype, as well as his parents were recruited. Whole-exome sequencing (WES) was performed on the proband and his parents. Two COQ4 variants, c.433C > T (p.Arg145Cys) and c.719G > T (p.Arg240Leu), were identified, among which c.719G > T (p.Arg240Leu) represented the first reported case in complicated hereditary spastic paraplegia (HSP), and c.433C > T (p.Arg145Cys) had been previously documented.

conclusionsOur case expanded the genotype of complicated HSPs caused by COQ4 compound heterozygous mutations. It highlighted that COQ4-related HSP may present with progressive gait disorder, spasticity, tremor, and distinct exercise-induced myalgia, underscoring the value of WES in diagnosing atypical pediatric spastic paraplegias.