A patient presents with progressive muscle weakness, ptosis, and diplopia. Which diagnosis is most likely and what is the targeted molecule?

• A. Myasthenia Gravis; autoantibodies attack acetylcholine receptors
• B. Systemic lupus erythematosus; autoantibodies attack a wide variety of cells in the body (cell surface, cytoplasm, and nuclear proteins)
• C. Multiple sclerosis; autoantibodies attack myelin
• D. Guillain-Barré syndrome; autoantibodies attack peripheral nerves

Answer: (A)

Progressive, fatigable weakness with ptosis and diplopia points to a neuromuscular junction problem. In myasthenia gravis, autoantibodies target the postsynaptic nicotinic acetylcholine receptors at the motor end plate, decreasing receptor density and impairing the ability of acetylcholine signaling to trigger a sufficient end-plate potential. With repeated use, receptors are further blocked or removed, so muscle contraction weakens over time and improves after rest. The molecule targeted is the postsynaptic acetylcholine receptor on the muscle membrane. Treatments that increase acetylcholine at the synapse, such as acetylcholinesterase inhibitors, improve weakness, supporting this mechanism. Other listed diseases involve different targets—autoantibodies against a wide array of cellular components in lupus, demyelination in the central nervous system in multiple sclerosis, or peripheral nerve components in Guillain-Barré—and don’t produce the same fatigable ocular weakness pattern.