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A recombinant-expression cassette is constructed for the gene MOCS1 which via alternative splicing, facilitates the expression of the proteins MOCS1A and MOCS1B, both of which are necessary for the formation of a first intermediate, cyclic pyranopterin monophosphate within the biosynthetic pathway leading to active molybdenum cofactor (MoCo). A recombinant adeno-associated virus vector is used to express the artificial MOCS1 minigene to cure the lethal MOCS1-deficient phenotype.

Homozygosity mapping and two consanguineous affected Israeli-Arab families with five patients was used to link a molybdenum cofacor deficiency (MoCoD) gene to an 8-cM region on chromosome 6p21.3 between markers D6S1641 and D6S1672. MoCoD is a fatal disorder which is evident shortly after birth. There is mental retardation with profound neurological abnormalities, and there are severe seizures unresponsive to therapy. Existence of at least two complementation groups indicates genetic heterogeneity.