Liver Pathology in Mitochondrial Complex I Deficiency from Bi-Allelic Mutations in NDUFS2: A Report of Findings at Autopsy

Background: Mitochondriopathies are a heterogeneous group of genetic disorders with a wide array of symptomatology, organ system involvement, and inheritance patterns. Neonatal presentation can be fatal with neuromuscular dysfunction, lactic acidosis and hepatic failure. Historic literature has numerous phenotypic illustrations; however, genotypic correlation is limited. With improved testing methods, genotype–phenotype correlation is now increasingly feasible as demonstrated herein. Case Report: We present liver pathology findings in an infant who expired with a diagnostic suspicion of a mitochondrial disorder. Postmortem hepatocyte hypereosinophilia with microvesicular steatosis associated with ultrastructural findings of mitochondrial hyperplasia supported a mitochondriopathy. Genetic testing eventually confirmed mitochondrial complex I deficiency from bi-allelic mutations in NDUFS2. Conclusions: Morphologic attributes can assist in diagnosis of mitochondriopathies before specific genetic testing results are available. This case also highlights that diagnostic information can be gained from ultrastructural examination of postmortem liver tissue.