Globoid cells, glial nodules, and peculiar fibrillary changes in the cerebro‐hepato‐renal syndrome of zellweger

Abstract

In addition to a distinct malformation (pachymicrogyria, heterotaxic lamination of the cerebellar cortex, olivary dysplasia), unusual degenerative changes were found in the nervous system of 2 unrelated babies with the Zellweger syndrome. Cerebral clefts were present in 1 case. In both infants there was neuron loss and accumulation of glial nodules and globoid cells in the gray matter as well as degeneration of the white matter. There was fatty change in astrocytes and diffuse gliosis. Neurons in the column of Clarke and the lateral cuneate nucleus showed peculiar fibrillary changes. Cytoplasmic inclusion bodies were seen in the spinal ganglia. Swelling of cortical astrocytes was remarkable in the older infant. The combination of a rare malformation with the cell changes described here gives the syndrome a unique neuropathological profile.

Disorders of Neuronal Migration

“…The four layer pattern is not found and microgyri also line the bottom of sulci, a phenomenon referred to as "cloverleaf microgyria". 107 Regions that appear macroscopically pachygyric in Zellweger syndrome are histologically almost similar to the microgyric regions. Both neurons and glial cells show light microscopic and ultrastructural changes in Zellweger syndrome and an impressive storage of lipid material of various types is seen in macrophages and astrocytes.…”

Neonatal adrenoleukodystrophy: New cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes

“…Numerous reviews of the neuropathology of ZS have documented several abnormalities of cerebral and cerebellar development that previously were thought to constitute a complex pathognomonic of ZS : micropachygyria, abnormal cortical laminations, heterotopias in cerebral and cerebellar white matter, olivary and dentate hypoplasia and dysplasia, and macrophage infiltration and destruction of the cerebellar molecular layer [Passarge and McAdams, 1967;Opitz et al, 1969;Agamanolis et al, 1976;Mej Liu et al, 1976;DeLeon et al, 1977;Evrard et al, 19781. However, as described above, most of these abnormalities have also been found in children with NALD, but usually to a milder degree.…”

Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum

“…Patients with ZS, the most severe ZSDs, generally die before reaching the age of 1 yr. The CNS pathological features of patients with ZS include migration defects in cortical neurons, abnormal dendritic arborization of Purkinje cells, and dysplastic alterations of inferior olivary nuclei (ION) ( Volpe & Adams, 1972 ; de León et al, 1977 ; Evrard et al, 1978 ; Steinberg et al, 2006 ). The biochemical abnormalities, including marked reduction of plasmalogens, accumulation of VLCFAs, and reduction in the level of docosahexaenoic acid (DHA) ( Weller et al, 2003 ), are thought to be relevant to the manifestations of malformations in the CNS.…”