General description

Molybdenum cofactor deficiency (MOCOD) is a rare autosomal recessive disorder caused by pathogenic variants in genes such as MOCS1, MOCS2, and GPHN, which are involved in molybdenum cofactor biosynthesis. This cofactor is essential for the activation of several enzymes, including sulfite oxidase, xanthine oxidase, and aldehyde oxidase. The deficiency leads to a loss of function in these enzymes, resulting in the accumulation of toxic metabolites such as sulfite, xanthine, and hypoxanthine, which contribute to widespread neurological damage and other systemic effects.

Clinically, MOCOD manifests in the neonatal period with severe symptoms, including intractable seizures that do not respond to standard treatments, feeding difficulties, and significant neuromotor abnormalities. Affected infants often exhibit fluctuating muscle tone, dystonic movements, spastic quadriplegia, and an exaggerated startle reflex (hyperekplexia). Progressive microcephaly and severe global developmental delay, including the inability to sit or speak, are commonly observed. Additionally, some cases present with coarse facial features and lens dislocation.

Biochemical hallmarks of MOCOD include hypouricemia due to reduced uric acid production, along with elevated urinary levels of sulfite, xanthine, and S-sulfocysteine. These abnormalities can lead to complications such as xanthine stone formation in the urinary tract. The accumulation of sulfite further contributes to the disease's severe neurological impact, leading to a poor prognosis.

Differential diagnosis

A related disorder, Sulfite oxidase deficiency (SOD), arises from mutations in the sulfite oxidase gene (SUOX). Since molybdenum cofactor is essential for sulfite oxidase function, its deficiency results in a clinical presentation similar to sulfite oxidase deficiency. It is difficult to distinguish sulfite oxidase deficiency and molybdenum cofactor deficiency on imaging.

References

1. Durmaz, Mehmet Sedat, and Bora Özbakır. "Molybdenum cofactor deficiency: neuroimaging findings." Radiology Case Reports 13.3 (2018): 592-595.