Lipid alterations in human brains in phenylketonuria

Abstract

Four areas of white matter from the brains of 3 patients with phenylketonuria[long dash]9, 19, and 30 years of age[long dash]were histologically and chemically analyzed along with controls. Histologic studies disclosed spongy or demyelinating lesions, the former predominating in younger and the latter, in older persons. In 2 samples taken from the oldest patient, extensive demyelination correlated with severe lipid defects with disproportionately greater loss of mono- and polyunsaturated fatty acids. In samples from spongy areas of younger patients, there were more moderate lipid defects but with preferential deficit of cerebrosides and of cerebronic acid. Neither histologic nor chemical data suggest uniformity of chemical or histologic pathology. A multiplicity of factors appears to be related to the pathology of white matter in phenylketonuria: deficit or inhibition of fatty acid desaturating enzymes, impairment of lipid attachment sites, and loss of lipids preferentially affecting those with long-chain fatty acid components, as seen in other demyelinating conditions.