Researchers at Great Ormond Street Hospital, London, UK examined the clinical, brain MRI, biochemical, genetic, and EEG features and outcome in 8 children with a diagnosis of molybdenum cofactor deficiency seen over a 10-year period. Six neonates had an early (classical) onset with predominantly epileptic encephalopathy and neonatal seizures, and 2 had a late (atypical) onset with global developmental impairment. Four were boys. Neonatal history was normal except in one infant with presumed HIE who required ventilatory support for 3 days. Age at presentation ranged from 1 day to 24 months. Clinical features leading to diagnosis included progressive microcephaly, dysmorphisms, progressive pyramidal and extrapyramidal signs, axial hypotonia, kyphoscoliosis, verbal dyspraxia, and visual impairment due to cortical damage or lens subluxation. Follow-up ranged from 12 months to 8 years. No patient died. Time to biochemical diagnosis (high urine sulfite and low plasma urate, high urine purine metabolites [xanthines] and 5-sulfocysteine) ranged from 4 days to 4 years (median 3 months). EEG abnormalities included burst suppression pattern and seizure activity. Brain MRI showed cerebral infarction in all except one with atypical onset. Distinctive features seen in an early brain MRI were acute infarction of the globus pallidi and subthalamic regions with older cerebral hemisphere infarction, chronic lesions suggestive of a prenatal insult, pontocerebellar hypoplasia and retrocerebellar cyst, and a band at the cortical/subcortical white matter. Sequential imaging showed progressive pontine atrophy and enlargement of retrocerebellar cyst. Early brain MRI (<1 week) abnormality may lead to early diagnosis and treatment. [1]

COMMENT. Molybdednum cofactor deficiency is a rare autosomal recessive neurodegenerative disorder characterized by deficiency of molybdenum-dependent enzymes xanthine oxidase, sulfite oxidase, nitrogenases, and nitrate reductase. Presentation includes intractable seizures, severe global delay, feeding difficulties, followed by frequent infant fatalities. Milder phenotypes are described with late presentation and more sanguine prognosis. The above description of a specific MRI pattern may lead to early prenatal diagnosis, mutational confirmation and therapeutic intervention.