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 MOCS2. 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 showing 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.16 C > 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 genetic spectrum of MoCD-B by identifying for the first time a novel MOCS2 variant (c.257G > T, p.Ser86Ile). In infants, acute neurological deterioration after infection accompanied by persistent hypouricemia and bilateral globus pallidus lesions should prompt consideration of mild MoCD-B. Our observations do not provide sufficient evidence to support routine immunotherapy for MoCD-B patients after SARS-CoV-2 infection; treatment management should be guided by established recommendations for COVID-19–associated neurological complications. CLINICAL TRIAL NUMBER: Not applicable.