MoCD type A is among a class of genetic disorders known as inborn errors of metabolism. It is an ultra-rare pediatric disease with an autosomal recessive pattern of inheritance.
MoCD is characterized by the disruption of the biosynthesis pathway that normally produces an essential substance known as molybdenum cofactor (MoCo). MoCo enables function of certain essential enzymes, including sulfite oxidase (SO).
However, in patients with MoCD type A, an error in the MOCS1 gene prevents the body from producing MoCo. In healthy individuals, biosynthesis of MoCo involves converting guanosine triphosphate (GTP) to cyclic pyranopterin monophosphate (cPMP). In patients with MoCD type A, this process does not happen as it should, and cPMP is not created. Thus, MoCo is not produced at required levels. To the right is a representation of the molybdenum cofactor biosynthesis pathway and the impact of the three variants of MoCD on MoCo synthesis.
Deficiency in MoCo results in reduced activity of three key enzymes: sulfite oxidase, xanthine oxidoreductase and aldehyde oxidase. Decreased activity of sulfite oxidase is believed to be the causative factor behind the severe and rapidly progressive central nervous system damage seen in patients with MoCD, as sulfite oxidase normally degrades highly toxic sulfite through conversion to sulfate. With increased levels of sulfite, S-sulfocysteine (SSC), typically low or undetectable in healthy children, accumulates, resulting in brain injury. Below shows a portion of the metabolic pathway in a healthy child and changes in the pathway with MoCD Type A.