Two Mild Phenotype Molybdenum Cofactor Deficiency Patients with Novel MOCS2 Mutation and Immunological Treatment after COVID-19 Infection

Background Molybdenum cofactor deficiency type B (MoCD-B) is a rare autosomal recessive metabolic disorder caused by mutations in the MOCS2 gene. Patients with mild phenotypes may experience infection-related neurological deterioration followed by partial spontaneous recovery. This study presents the first reported cases of acute encephalopathy triggered by SARS-CoV-2 infection in patients with mild MoCD-B and provides clinical insights into the course of neurological symptoms and corresponding interventions. Methods Clinical and genetic information were collected from two patients showed acute encephalopathy, each harboring mutated molybdenum cofactor synthesis gene 2 ( MOCS2 ). Results Both patients developed acute encephalopathy following SARS-CoV-2 infection. Clinical manifestations included motor regression, dystonia, and brain MRI abnormalities predominantly involving the bilateral globus pallidus and cerebral peduncles. Biochemical testing revealed persistently low serum uric acid and hypohomocysteinemia. Immunological analysis showed positive thyroid autoantibodies. Cerebrospinal fluid (CSF) analysis indicated elevated levels of interleukin-8 and other pro-inflammatory cytokines during the acute phase. Whole-exome sequencing identified a known pathogenic variant (c.16C > T, p.Gln6Ter) and a novel missense variant (c.257G > T, p.Ser86Ile) in MOCS2 . Both patients received immunotherapy with intravenous immunoglobulin (IVIG) and methylprednisolone, resulting in gradual symptom improvement. Conclusion This study expands the clinical and genetic spectrum of MoCD-B by identifying a novel MOCS2 variant (c.257G > T, p.Ser86Ile). In infants, infection-related neurological deterioration with persistent hypouricemia and bilateral globus pallidus lesions should raise suspicion for mild MoCD-B. The observed IL-8 elevation during SARS-CoV-2–associated exacerbations, along with temporal symptomatic improvement after immunotherapy, suggests a possible neuroinflammatory mechanism. These findings suggest that immunotherapy may be beneficial when infection-related encephalopathy is accompanied by neuroinflammatory evidence and underscore the importance of preventing SARS-CoV-2 exposure in this high-risk population. Clinical trial number Not applicable.