Cortical dysgenesis in a variant of phenylketonuria (dihydropteridine reductase deficiency)

The neuropathology of a 2 1/2-year-old patient with dihydropteridine reductase deficiency showed diffuse demyelination throughout white matter and spongy vacuolation in the long tracts of the brain stem. These changes are characteristic neuropathologic observations in untreated phenylketonuria. In addition, extensive neuronal loss, calcification and abnormal vascular proliferation were noted in the cerebral cortex, white matter, basal ganglia, and thalamus. Golgi studies demonstrated an abnormal orientation of neurons together with abnormalities of dendrites and dendritic spines. The pathogenesis of the vascular abnormalities in this condition is unknown, although folate deficiency may be involved. The secondary deficiency of serotonin and dopamine occurring during neuronal growth and differentiation may also affect the terminal stages of neuronal maturation.