Subjects:Developmental/Behavioral Health, Genetics, Growth/Development Milestones
Topics:combined molybdoflavoprotein enzyme deficiency, developmental delay, fosdenopterin, xanthine, creatinine, uric acid, hypoxanthine, genes
Molybdenum cofactor deficiency (MoCD) is a rare, autosomal recessive disorder caused by a reduced availability of molybdenum cofactor that leads to toxic accumulations of sulfite and consequent neurologic damage. Compared with the typically dramatic presentation of early disease MoCD with seizures and encephalopathy, late-onset MoCD presentation may be subtle and manifest in older infants and young children as nonspecific developmental delays and a nonspecific array of other signs and symptoms.1 ,2

Defects in molybdenum cofactor formation arise from biallelic pathogenic variants in 1 of 3 molybdenum cofactor synthesis (MOCS) genes or GPHN encoding gephyrin. MOCS begins with conversion of guanosine triphosphate to cyclic pyranopterin monophosphate (cPMP). Lacking cPMP, downstream cofactor synthesis is disrupted (Fig 1).1 Only patients with pathogenic variants in MOCS1 (referred to as MoCD type A) respond effectively to cPMP replacement therapy. Early diagnosis, identification of genetic subtype, and prompt initiation of cPMP in patients with MoCD type A is crucial to prevent irreversible central nervous system damage.