Neuropathology of Methylmalonic Acidemia in a Child

Methylmalonic acidemia is a rare disease, and its neuropathology in childhood has been rarely reported. A 3-year-old male with vitamin B 12 nonresponsive type of methylmalonic acidemia developed repeated attacks of acidemia associated with common cold since neonatal age. Psychomotor development was markedly delayed, and he died of a severe attack of acidemia. Postmortem examination disclosed marked brain atrophy with old lesions of hypomyelination, granule cell reduction, and spongy changes scattered in the cerebral cortex, white matter, brainstem nuclei, and cerebellar cortex, and accompanied by recent lesions of multiple small hemorrhagic and necrotic foci in the caudate nucleus, cerebellum, and brainstem. Neuron reduction without astrogliosis in the cerebellum, brainstem, and hippocampus, and the association of single-stranded DNA-positive cells in the brainstem and cerebellar nuclei were demonstrated. These findings, and karyorrhexis in the neonatal brains described in the literature, suggest that repeated episodes of cell death with apoptosis occur in association with attacks of acidosis beginning in the neonatal period in methylmalonic acidemia.