Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalitiesin the cat model of alpha-mannosidosis

Alpha-mannosidosis is a disease caused by the deficient activity of alpha-m annosidase, a lysosomal hydrolase involved in the degradation of glycoprote ins. The disease is characterized by the accumulation of mannose-rich oligo saccharides within lysosomes. The purpose of this study was to characterize the peripheral nervous system (PNS) and central nervous system (CNS) myeli n abnormalities in cats from a breeding colony with a uniform mutation in t he gene encoding alpha-mannosidase. Three affected cats and 3 normal cats f rom 2 litters were examined weekly from 4 to 18 wk of age. Progressively wo rsening neurological signs developed in affected cats that included tremors , loss of balance. and nystagmus. In the PNS, affected cats showed slow mot or nerve conduction velocity and increased F-wave latency. Single nerve fib er teasing revealed significant demyelination/remyelination in affected cat s. Mean G-ratios of nerves showed a significant increase in affected cats c ompared to normal cats. Magnetic resonance imaging of the CNS revealed diff use 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 com pared to normal cats. consistent with myelin abnormalities. Histology confi rmed myelin loss throughout the cerebrum and cerebellum. Thus, histology, e lectrodiagnostic testing, and magnetic resonance imaging identified signifi cant myelination abnormalities in both the PNS and CNS that have not been d escribed previously in alpha-mannosidosis.