Development of Myelin in Inherited Disorders of Amino Acid Metabolism

IN 1950, Alvord et al1first suggested that the principal neuropathological feature of phenylketonuria (PKU) was a delay in the development of myelin. Subsequently, other investigators described areas of pallor in sections of central white matter stained for myelin and retarded myelination of the long tracts.2,3Similar abnormalities were found in maple syrup urine disease (MSUD).4-6Biochemical investigations of the cerebral white matter of patients with these diseases have also indicated that myelin was accumulating at a slower rate than that found in normal brains. In both PKU and MSUD, the water content of cerebral white matter was increased and the lipid content reduced.7-10The reduction of cerebrosides exceeded that of other lipid classes,9-11which is to be expected, since the accumulation of this lipid most closely parallels the formation of normal myelin.12 While biochemical studies of this type confirmed prior histological observations,