Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome

Childhood ataxia with diffuse central nervous system hypomyelination syndro me (CACH) is a recently described leukodystrophy of unknown etiology. To ch aracterize the neuropathological features and gain insight as to the pathog enesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with "foamy" cyt oplasm, small round nuclei and fine chromatin. Electron microscopy (EM) rev ealed cells in the white matter with abundant cytoplasm containing many mit ochondria and loosely clustered, membranous structures, but lacking the lys osomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells wit h abundant cytoplasm labeled with oligodendroglial markers, but did not rea ct with macrophage or astrocytic markers. Double immunolabeling with macrop hage and oligodendroglial markers clearly distinguished macrophages from th e "foamy" oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Nor mal and pathological brain control tissues did not contain FODCs. These neu ropathological findings will be useful pathological identifiers of CACH, an d may provide clues to the pathogenesis of this disorder.