title: Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalities in the cat model of alpha-mannosidosis.
abstract: Alpha-mannosidosis is a disease caused by the deficient activity of alpha-mannosidase, a lysosomal hydrolase involved in the degradation of glycoproteins. The disease is characterized by the accumulation of mannose-rich oligosaccharides within lysosomes. The purpose of this study was to characterize the peripheral nervous system (PNS) and central nervous system (CNS) myelin abnormalities in cats from a breeding colony with a uniform mutation in the gene encoding alpha-mannosidase. Three affected cats and 3 normal cats from 2 litters were examined weekly from 4 to 18 wk of age. Progressively worsening neurological signs developed in affected cats that included tremors, loss of balance, and nystagmus. In the PNS, affected cats showed slow motor nerve conduction velocity and increased F-wave latency. Single nerve fiber teasing revealed significant demyelination/remyelination in affected cats. Mean G-ratios of nerves showed a significant increase in affected cats compared to normal cats. Magnetic resonance imaging of the CNS revealed diffuse white matter signal abnormalities throughout the brain of affected cats. Quantitative magnetization transfer imaging showed a 8%-16% decrease in the magnetization transfer ratio in brain white matter of affected cats compared to normal cats, consistent with myelin abnormalities. Histology confirmed myelin loss throughout the cerebrum and cerebellum. Thus, histology, electrodiagnostic testing, and magnetic resonance imaging identified significant myelination abnormalities in both the PNS and CNS that have not been described previously in alpha-mannosidosis.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Vite
authors.forename: J C
authors.initials: JC
authors.lastname: McGowan
authors.forename: K G
authors.initials: KG
authors.lastname: Braund
authors.forename: K J
authors.initials: KJ
authors.lastname: Drobatz
authors.forename: J D
authors.initials: JD
authors.lastname: Glickson
authors.forename: J H
authors.initials: JH
authors.lastname: Wolfe
authors.forename: M E
authors.initials: ME
authors.lastname: Haskins
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002415:Cats; D004576:Electromyography; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000473:pathology*; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology*; D008363:alpha-Mannosidosis / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*