Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome: neuropathological and biochemical study of two cases

We report neuropathological, biochemical and molecular studies on two patie nts with childhood ataxia with diffuse central nervous system hypomyelinati on (CACH) syndrome, a leukodystrophy recently defined according to clinical and radiological criteria. Both had severe cavitating orthochromatic leuko dystrophy without atrophy, predominating in hemispheric white matter, where as U-fibers, internal capsule, corpus callosum, anterior commissure and cer ebellar white matter were relatively spared. The severity of white matter l esions contrasted with the rarity of myelin breakdown products and astrogli al and microglial reactions. In the white matter, there was an increase in a homogeneous eel population with the morphological features of oligodendro cytes, in many instances presenting an abundant cytoplasm like myelination glia. These cells were negative for glial fibrillary acidic protein and ant ibodies PGM1 and MIB1. Some were positive for myelin basic protein, proteol ipid protein (PLP), and myelin oligodendrocyte glycoprotein, but the majori ty were positive for human 2'-3' cyclic nucleotide 3' phosphodiesterase and all were positive for carbonic anhydrase II, confirming that they are olig odendrocytes. Myelin protein and lipid content were reduced. The PLP gene, analyzed in one case, was not mutated or duplicated. The increased number o f oligodendrocytes without mitotic activity suggests an intrinsic oligodend roglial defect or an abnormal interaction with axons or other glial cells. This neuropathological study supports the notion that CACH syndrome constit utes a specific entity.