There are two ways to classify neuromuscular diseases. The first relies on its mechanism of action, or how the action of the diseases affects normal<unk> ing (whether it is through mutations in genes or more direct pathways such as poisoning). This category divides neuromuscular diseases into three broad categories: immune-mediated disease, toxic/metabolic and congenital syndromes. The second classification method divides the diseases according to the location of their disruption. In the neuromuscular<unk> , the diseases will either act on the presynaptic membrane of the motor neuron, the synapse separating the motor neuron from the muscle fiber, or the postsynaptic membrane (the muscle fiber). Immune-mediated Immune-mediated diseases include a variety of diseases not only affecting the neuromuscular<unk> . Immune-mediated disorders range from simple and common problems such as allergies to disorders such as HIV/AIDS. Within this classification, autoimmune disorders are considered to be a subset of immune-mediated syndromes. Autoimmune diseases occur when the body's immune system begins to target its own cells, often causing harmful effects. The<unk> s present within this subset are myasthenia gravis, and Lambert-Eaton syndrome.(reference 26) In each of these diseases, a receptor or other protein essential to normal<unk>  of the<unk>  is targeted by antibodies in an autoimmune attack by the body. Toxic/metabolic Metabolic diseases are usually a result of abnormal<unk> ing of one of the metabolic processes required for regular production and utilization of energy in a cell. This can occur by damaging or disabling an important enzyme, or when a feedback system is abnormally<unk> ing. Toxic diseases are a result of a form of poison that effects neuromuscular<unk> <unk> ing. Most commonly animal venom or poison, or other toxic substances are the origin of the problem.<unk> s in this category include snake venom poisoning, botulism, arthropod poisoning, organophosphates and hypermagnesemia.(reference 13) Organophosphates are present in many insecticides and herbicides. They are also the basis of many nerve gases.(reference 27) Hypermagnesmia is a condition where the balance of magnesium in the body is unstable and concentrations are higher than normal baseline values.(reference 28) Congenital Congenital syndromes affecting the neuromuscular<unk>  are considered a very rare form of disease, occurring in 1 out of 200,000 in the United Kingdom.(reference 29) These are genetically inherited disorders. Symptoms are seen early since the affected individuals carry the mutation from birth. Congenital syndromes are usually classified by the location of the affected gene products. Congenital syndromes can have multiple targets affecting either the presynaptic, synaptic or postsynaptic parts of the neuromuscular<unk> .(reference 30) For example, if the malfunctioning or inactive protein is acetylcholinesterase, this would be classified as a synapse congenital syndrome.(reference 29) Presynaptic The diseases that act on the presynaptic membrane are autoimmune neuromyotonia, Lambert–Eaton syndrome, congenital myasthenia gravis and botulism.(reference 5) All of these disorders negatively affect the presynaptic membrane in some way. Neuromyotonia causes antibodies to damage the normal<unk>  of potassium rectifier channels, while Lambert–Eaton syndrome causes antibodies to attack presynaptic calcium channels.(reference 7) Congenital myasthenia gravis is a large group of diseases, since the genetic defects can affect any point in the chain of events leading to successful transmission across the<unk> . One discovered type of congenital myasthenia gravis can affect the<unk>  presynaptically by a mutation in the gene encoding choline acetyl transferase.(reference 29) This protein is an enzyme that is responsible for catalyzing the reaction that combines acetyl-coenzyime A with choline, yielding acetylcholine.(reference 31) There are many mechanisms through which presynaptic<unk>  can be impaired. Most often this causes a decrease in the release of acetylcholine. It can also impair vesicle exocytosis by interfering with the complex guiding vesicle fusion and release of contents. Mechanism of action can also impair the calcium channels that induce exocytosis of the vesicles. Other ion channels can also be disrupted, such as the potassium channels causing inefficient repolarization at the presynaptic membrane as in neuromyotonia.(reference 5) Synapse At the synaptic cleft, the neurotransmitter normally diffuses across the synapse to eventually contact postsynaptic receptors. However, after exiting the presynaptic membrane, the neurotransmitters can be hindered by a subset of diseases that interfere with the transmission of the neurotransmitter across the synapse. The mechanism currently known that operates via the synaptic cleft causing impairment of normal<unk> ing is another congenital myasthenia gravis.(reference 7) This mechanism is the only currently known disease that acts on the synapse.(reference 12) It acts by impairing the<unk>  of the enzyme that breaks down acetylcholine causing it to become very hypertonic at the synapse.(reference 12) This increase in acetylcholine in the synapse disrupts normal<unk> ing of the<unk> ,.(reference 32)(reference 33) Postsynaptic The highest number of diseases affect the neuromuscular<unk>  postsynaptically. In other words, it is the most susceptible to negative intervention.(reference 7) The targets of these postsynaptic diseases can be multiple different proteins. Immune-mediated myasthenia gravis being the most common, effecting the acetylcholine receptors at the post synaptic membrane.(reference 35) All the diseases that affect the postsynaptic membrane are forms of myasthenia gravis.(reference 5) Here is a list of the diseases: myasthenia gravis, neonatal myasthenia gravis, drug-induced myasthenia gravis and several types of Congenital myasthenia where the product of the mutated gene is a postsynaptic protein (reference renamed from 5)
Neuromuscular junction disease
Neurocristopathy
Neuromuscular disease
Neurolathyrism
Upper motor neuron lesion
Basal ganglia disease
Lower motor neuron lesion
Congenital myopathy