Periodic paralysis
Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis (rarely death) from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move (a channelopathy).
It should be noted that the symptoms of periodic paralysis can also be caused by hyperthyroidism; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.

# Types
Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent need carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:
- Hypokalemic periodic paralysis (Online Mendelian Inheritance in Man (OMIM) 170400), where potassium leaks into the muscle cells from the bloodstream.
- Hyperkalemic periodic paralysis (Online Mendelian Inheritance in Man (OMIM) 170500), where potassium leaks out of the cells into the bloodstream.
- Paramyotonia congenita (Online Mendelian Inheritance in Man (OMIM) 168300), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down.
- Andersen-Tawil syndrome (Online Mendelian Inheritance in Man (OMIM) 170390), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosis (curvature of the spine), webbing between the second and third toes or fingers (clinodactyly), crooked fingers, a small jaw (micrognathia) and low-set ears.

# Diagnosis
This disease is unusually difficult to diagnose. Patients often report years of wrong diagnosis and treatments that made them worse instead of better. Part of this may be that migraines are present in up to 50% of patients and can cause a confusing array of symptoms including headaches, speech difficulties and visual, auditory or sensory auras. DNA testing is available for only a half dozen common gene mutations, while dozens of known mutations are possible but are not routinely tested. EMG results will be normal except during attacks. A properly performed Exercise EMG (Compound Muscle Amplitude Potential Test) can provide an accurate diagnosis in better than 80% of cases. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used.
Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis. These diseases are not the same as having a very low level of potassium (hypokalemia) or high potassium (hyperkalemia) and must not be treated as such. The total body store of potassium is usually normal; it is just in the wrong place.

# Treatment
Treatment of the periodic paralyses usually includes carbonic anhydrase inhibitors (such as acetazolamide or dichlorphenamide), taking supplemental oral potassium chloride (for hypos) or avoiding potassium (for hypers), thiazide diuretics to manipulate the amount of potassium retained by the kidneys, and significant lifestyle changes including tightly controlled levels of exercise or activity.  However, the exact gene mutation, the ion channel affected, and the amount of genetic change or expression can have significant impact on disability and treatment.
Treatment of ATS is similar to that for periodic paralysis, with dichlorphenamide the drug of first choice. Pacemaker insertion or an implantable cardioverter-defibrillator may be required to control cardiac symptoms.

# Prognosis
While the disability can range from minor, occasional weakness to permanent muscle damage, inability to hold a normal job and use of a powerchair, most people function fairly well with drugs and lifestyle changes. On a lighter note, people with periodic paralysis are sometimes lovingly called "Possum" because they "play dead" (i.e., become paralyzed) when startled or stressed.