Abstract / Summary
Purpose To describe the clinical and neuroimaging features of mitochondrial complex III deficiency, nuclear type 8 (MC3DN8), associated with a recurrent leucine tyrosine arginine motif protein 7 (LYRM7) variant, and to place these findings in the context of the existing literature. Methods We describe three pediatric patients from two consanguineous Roma families who carried the homozygous LYRM7 variant c.73G>A [p.(Asp25Asn)]. Clinical, neuroimaging, and genetic data were analyzed and supplemented by a review of previously reported MC3DN8 cases. Results Clinical manifestations ranged from global developmental delay to progressive neurological impairment with spasticity and severe metabolic decompensation. Prominent ophthalmological features included cortical blindness and intermittent amaurosis. Brain magnetic resonance imaging consistently demonstrated multifocal cavitating leukoencephalopathy. Review of 18 previously reported cases showed marked phenotypic variability, ranging from severe early-onset disease with metabolic decompensation to asymptomatic presentation or early death. Conclusion MC3DN8 is characterized by marked clinical heterogeneity. Genetic testing is essential for diagnosis, and further studies are needed to clarify genotype–phenotype correlations and improve disease management.