Axonal polyneuropathy: compound heterozygous mutations in NDUFS1—a case report

Abstract Background Children presenting with progressive gait abnormality may suffer from a genetic disorder. NDUFS1-related mitochondrial complex I deficiency is a rare disorder with highly variable phenotypes. Predominant axonal neuropathy without prominent systemic metabolic dysfunction is unusual. Expanding reports of such presentations is important for accurate diagnosis. Case presentation A young adolescent boy with non-consanguineous parents presented with an atypical and severe axonal sensorimotor polyneuropathy. His metabolic workup was negative. Molecular genetic analysis uncovered a rare form of mitochondrial complex I deficiency due to compound heterozygous variants of the NDUFS1 gene. Conclusions This case highlights a rare and atypical presentation associated with two NDUFS1 variants, one previously annotated as variant of uncertain significance in ClinVar. The other is novel. This expands the phenotypic and genetic spectrum linked to NDUFS1 -related disorders.