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Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
This is an autosomal recessive disease caused by a mutation of the GALC gene which encodes for galactocerebrosidase (GALC). The deficiency of this lysosomal enzyme leads to the accumulation of several sphingolipids, including galactosylceramide and psychosine, which result in oligodendrocyte death and demyelination. Disease frequency is 1:100,000, and 1:150 carriers. Males and females are equally affected. Onset is in infancy (90%) to the fifth decade (10% juvenile to adult).
Neural Stem Cells and Oligodendrocyte Progenitors in the Central Nervous System
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Jennifer A. Jackson, Diana L. Clarke
Oligodendrocyte progenitors have been characterized in rodent species by their bipolar morphology and by the presence of specific markers. In vitro studies as well as in vivo experiments have shown that these cells are actively proliferating and posses migratory properties. Oligodendrocyte progenitors arise from multipotential cells in spatially restricted germinal zones thoughout the brain and spinal cord. These progenitors migrate long distances away from these zones in the CNS before they settle along fiber tracts of the future white matter and then transform into preoligodendrocytes. The pre-oligodendrocyte is a multiprocessed, post-migratory cell that retains the ability to divide but is not responsive to the mitogen, platelet-derived growth factor (PDGF).32-34 These cells can be identified by their acquisition of the marker, 04.35 The preoligodendrocyte can further differentiate into an immature oligodendrocyte, characterized in the rat by the appearance of the marker GalC, and the loss of expression of GD3 and A2B5 antigens on the cell surface. CNP (2’,3’-cyclic nucleotide 3’-phosphodiesterase), the earliest known myelin-specific protein to be synthesized by developing oligodendrocytes also appears at this time.
Radiation-induced neuropathological changes in the oligodendrocyte lineage with relevant clinical manifestations and therapeutic strategies
Published in International Journal of Radiation Biology, 2022
Upon differentiation into preoligodendrocytes, PDGFRα expression declines (May et al. 2014) and these cells start to express galactosylceramide/sulfatides and pro-oligodendroblast antigen (POA), both of which are recognized by the O4 antibody (Deng and Poretz 2003; Jantzie et al. 2013). They become post-migratory, but remain proliferative (Grinspan and Franceschini 1995) while gaining morphological complexity. Subsequently, preoligodendrocytes further differentiate into less proliferative, immature non-myelinating oligodendrocytes that express galactocerebroside (GalC or O1) (Ono et al. 2001; Yang et al. 2011). In addition, immature oligodendrocytes express 2′-3-cyclic nucleotide 3′-phosphodiesterase (CNPase), an early myelin marker (Gottle et al. 2015) that continues to be expressed in mature myelin (Verrier et al. 2013), as well as G-protein coupled receptor 17 (GPR17) (Fumagalli et al. 2011). These immature oligodendrocytes possess increased number of processes and extensions protruding from their cell bodies (See et al. 2004).
Genetic diseases mimicking multiple sclerosis
Published in Postgraduate Medicine, 2021
Chueh Lin Hsu, Piotr Iwanowski, Chueh Hsuan Hsu, Wojciech Kozubski
Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive leukodystrophy caused by deficient galactosylceramidase (GALCase) activity as a result of mutations in the GALC gene. The resulting unmetabolized galactolipids build up and are directly toxic to oligodendrocytes and Schwann cells, which manifests as progressive neurodegenerative symptoms including loss of vision, hearing, seizures, and premature death [73]. The newborn initial screening test of GALC enzyme activity is usually conducted to detect Krabbe disease. However, low levels of GALC enzyme activity cannot indicate the clinical type and the course of the disease. The genetic testing of Krabbe disease should be taken to confirm the diagnosis [73]. The four clinical types are classified by the age of onset [74], of which adult- onset Krabbe disease (AOKD) is of particular interest in this discussion due to its similar clinical pictures to MS [75].
A new compound heterozygous mutation in adult-onset Krabbe disease
Published in International Journal of Neuroscience, 2020
Xianghe Meng, Yingjiao Li, Yajun Lian, Yujuan Li, Liyuan Du, Nanchang Xie, Cui Wang
GALC is a lysosomal hydrolase involved in the degradation of galactosylceramide and almost all of the galactosylceramides are present in the myelin sheath [17]. The deficiency of GALC leads to the abnormal accumulation of the cytotoxic metabolite, psychosine or galactosylsphingosine, which causes central white matter and peripheral nerve demyelination [18]. Deficiency of GALC enzyme activity is observed in almost all cases of KD [7]. However, there is a lack of consistent correlation between GALC enzyme activity and the age of onset or pathogenesis of KD [19–21]. Our patient’s GALC enzyme activity was significantly reduced and met the diagnostic criteria for KD. Most common MRI findings in patients with late-onset KD include involvement of the parietooccipital white matter, pyramidal tract, and corpus callosum. White matter changes visualized on MRI are often considered as a hallmark feature of KD [22]. Therefore, when patients are presented with symptoms of spastic paraplegia and white matter changes, especially if there are changes in its symmetrical distribution, KD should be suspected. However, a definitive diagnosis of KD requires additional examinations in some patients because the results of enzymatic activity and MRI findings could be inconclusive.