Sporadic Amyotrophic Lateral Sclerosis Due to a FUS P525L Mutation with Asymmetric Muscle Weakness and Anti-ganglioside Antibodies

Abstract

Amyotrophic lateral sclerosis (ALS) due to a fused in sarcoma (FUS) P525L mutation is characterized by a rapidly progressive course. Multifocal motor neuropathy (MMN) may resemble ALS in early stage and is associated with anti-ganglioside antibodies. A 38-year-old woman was admitted to our hospital because of progressive muscle weakness in the right limbs. She had mild mental retardation and minor deformities. Initially, we suspected MMN given the asymmetric muscle weakness and detection of anti-ganglioside antibodies. However, physical and electrophysiological tests did not support MMN, instead suggesting ALS. We confirmed a heterozygous P525L mutation and finally diagnosed this case as ALS due to an FUS mutation.

Aberrant Ganglioside Functions to Underpin Dysregulated Myelination, Insulin Signalling, and Cytokine Expression: Is There a Link and a Room for Therapy?

“…Elevated levels of gangliosides GM1 and GM3 were found in the spinal cords of amyotrophic lateral sclerosis (ALS) patients, along with increased activities of enzymes mediating their hydrolysis [ 47 ]. Anti-ganglioside antibodies were found in a patient with ALS attributed to the P525L mutation in the fused in sarcoma (FUS) gene [ 48 ]. Thus, alterations of ganglioside metabolism accompany the much broader spectrum of neurological and psychiatric disorders that was accepted until recently.…”