Molybdenum cofactor deficiency - Phenotypic variability in a family with a late-onset variant

Abstract

In a family with molybdenum cofactor deficiency, the onset in the index case was delayed until 1 year of age, when the patient presented with an episode of lethargy and inconsolable crying culminating in a seizure. By 17 months she showed mild motor delay, regression in language skills, and feeding difficulties. Progressive global deterioration followed, associated with sustained irritability, dystonic posturing, and further seizures, before her condition subsequently plateaued. Low plasma uric acid, raised urinary xanthine and hypoxanthine, and positive urinary sulphite were found, which, coupled with assay of sulphite oxidase activity in cultured fibroblasts, confirmed the diagnosis. A sibling had isolated lens dislocation and an identical biochemical profile. MRI in both children was strikingly abnormal. Molybdenum cofactor deficiency may present as a late-onset variant with considerable phenotypic variability.