Pathophysiology of weakness in a patient with congenital end-plate acetylcholinesterase deficiency

A Japanese patient with congenital end-plate acetylcholine esterase (ACHE) deficiency developed severe proximal and truncal muscle weakness with preservation of distal strength. Electrophysiological studies included a train of stimuli at 3 Hz, which induced a marked decremental response in the deltoid but not in the first dorsal interosseous (FDI) muscle. Single fiber electromyography (EMG) revealed a high blocking rate (23.1 ± 30.5%, n = 13) with a markedly increased jitter (mean consectuve difference [MCD] 297 ± 218 ps) in the deltoid, but a low blocking rate (6.2 ± 7.4%, n = 16) despite an equally increased jitter (MCD 227 ± 147 μs) in the FDI. In vitro microelectrode study and computer simulation suggested that the combination of a large jitter and a low blocking rate may be ascribed to a reduced end-plate potential (EPP) amplitude with an abnormally prolonged decay time constant (τ). These characteristics may constitute the primary underlying pathophysiologic mechanism in our patient and in similar cases of congenital myasthenic syndrome.