Molybdenum Cofactor Deficiency

Abstract

Summary: Imaging findings in two children with molybdenum cofactor deficiency included, in one, diffuse low attenuation on CT in cerebral white matter, caudate nuclei, and thalami soon after birth. MR in both patients later demonstrated progressive widening of the sulci, ventricles, and cisterna magna, and loss of brain volume. MR finally showed cessation of myelination at 31 months and 16 weeks of age. Index terms: Children, diseases; Metabolic disorderMolybdenum cofactor deficiency is a rare hereditable metabolic disorder producing neurologic deterioration and death in early childhood. It is one of the diagnosable causes of neonatal seizures. We report the computed tomography (CT) and magnetic resonance (MR) findings in two children who were diagnosed with this disorder and followed at our institution. Case 1A full-term girl was the second child of nonconsanguinous parents, born to a healthy 23-year-old mother at an outside institution. The newborn appeared healthy at birth, but when she was less than 24 hours old, tremulousness, seizures, and lactic acidosis developed. Pharmacologic control of seizures was of limited success.Over the first few months of life, neurologic signs developed, including severe truncal hypotonia, poor head and motor control, limb contractures, and swallowing dysfunction. The head circumference, which was at the 90th percentile at birth, decreased progressively. At 7 months of age, the child's development was markedly delayed, being at the level of a 2 to 3 month old. Metabolic screening test results were normal, except for low serum uric acid. Normal muscle biopsy with oxidative enzyme studies excluded the diagnosis of a mitochondrial disorder. The diagnosis of molybdenum cofactor deficiency was made when results of repeated dipstick tests for urinary sulfite were positive.The child now has been followed through her second birthday. She is severely neurologically impaired and has no verbal expression. She has bilateral lens dislocation and no visual function. Her head circumference has dropped to the 10th percentile for age.Brain CT performed soon after birth was reported to be normal. MR was performed at our facility (1.5-T magnet) at 7 months of age. The ventricles appeared moderately enlarged, and the extracerebral spaces and cisterna magna were wide. The cerebral white matter width appeared decreased, with the depths of some sulci approaching the lateral ventricular margins. A subsequent examination at 23 months of age showed marked brain volume loss, with further widening of the sulci, cisterns, and ventricles. The interhemispheric fissure, anterior cerebral, and pericerebellar subarachnoid spaces were extremely dilated. Myelination was patchy, with absence of the expected T2 hypointensity of the white matter in some regions of the cerebrum and in the cerebellar hemispheres ( Figs 1A and B). Additionally, there were areas of signal abnormality on fast spin-echo long-repetition-time sequences (3500/34/1 and 3500/102/1 [repetition time/ echo time/excitations]). These included 6-to...