Molybdenum Cofactor Deficiency Presenting as Neonatal Encephalopathy: A Case Series

A BSTRACT Background: Molybdenum cofactor deficiency (MoCD) is a rare autosomal recessive inborn error of metabolism resulting in combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. It typically presents in the neonatal period with refractory seizures and progressive encephalopathy, often mimicking hypoxic-ischemic encephalopathy. Case Presentation: We report two term male neonates who presented with early-onset feeding difficulty, seizures, and neurological deterioration. Both had a history of unexplained sibling deaths. Neuroimaging demonstrated diffusion restriction and subsequent cystic encephalomalacia. Biochemical evaluation revealed markedly low serum uric acid levels, and metabolic studies confirmed molybdenum cofactor deficiency. Genetic analysis in one infant identified a pathogenic homozygous nonsense mutation in the MOCS2 gene, while the second case was biochemically confirmed, with subsequent parental carrier status demonstrated. Conclusion: MoCD is a rare but fatal cause of neonatal encephalopathy. Measurement of serum uric acid is a simple, inexpensive, and useful screening test in neonates with unexplained seizures. Early recognition facilitates genetic counseling and prenatal diagnosis in future pregnancies.