Vitamin B6-dependent seizures: pathology and chemical findings in brain

A 13 1/2-year-old child died with vitamin B6-dependent seizures in progress. Microscopic findings in brain included an abnormally sparse quantity of central myelinated fibers in the cerebral hemispheres. Glutamic acid concentrations were elevated and GABA concentrations reduced in the frontal and occipital cortices but not in the spinal cord. All other amino acid concentrations were normal, except for increased cystathionine in the occipital cortex. Pyridoxal-5-phosphate (PLP) was reduced in the frontal cortex. Glutamic acid decarboxylase activity comparable to that of controls was detected when the PLP concentration was greater than 0.05 mM. These findings suggest that pyridoxine-dependent seizures in man are associated with reduced GABA concentrations in the brain and with diminished central white matter structures.