A case report of MoCD etiology in a neonate: A novel homozygous MoCS2 variant.

Key Clinical Message: Molybdenum cofactor deficiency is a rare and fatal genetic disorder. Due to recurrence in the family, the etiological diagnosis could have impacted family planning and alertness to future offspring.

Abstract: Molybdenum cofactor deficiency (MoCD) is a rare and fatal genetic disorder that impairs molybdenum-dependent enzymes, resulting in conspicuous elevated urine sulfite levels and lowered serum uric acid levels. The disorder may be early-onset, causing high fatality in neonates due to secondary complications, or late-onset, manifesting in the first 2 years of life. Severe seizures, progressive neurological degeneration, motor abnormalities, and feeding difficulties are hallmarks of MoCD. Due to the similarity of clinical findings with those of sulfite oxidase deficiency and its neurological findings with hypoxic-ischemic encephalopathy, determining the true etiology remains challenging in MoCD patients. This case report presents a neonate in the first week of life with early onset refractory seizures, motor abnormalities, hypoactivity, and poor feeding behavior. Administering anti-epileptic drugs did not improve the patient's condition, who started decompensating further. Nevertheless, a thorough screening for metabolic disorders revealed low serum uric acid and high sulfite levels in the urine, indicating potential MoCD. A whole exome sequencing (WES) was thus consulted for confirmatory diagnosis. Unfortunately, the patient's WES results were received after his demise, revealing MoCD caused by a novel variant of the MoCS2 gene that has not yet been reported to the best of our knowledge. This case emphasizes the need to disseminate crucial information regarding MoCD and its etiologies for prompt molecular diagnosis to reduce morbidity and mortality.