A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release.
A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000172:deficiency*; D000293:Adolescent; D004576:Electromyography; D005071:Evoked Potentials; D006801:Humans; D008297:Male; D009045:Motor Endplate / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009132:Muscles / Q000201:enzymology; D009157:Myasthenia Gravis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration; D009469:Neuromuscular Junction / Q000201:enzymology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D013569:Synapses / Q000648:ultrastructure*; D009435:Synaptic Transmission
D011950:Receptors, Cholinergic; D000110:Acetylcholinesterase; D000109:Acetylcholine