General Periodic Paralysis FAQ
What are the Periodic Paralyses and what are the symptoms?
The periodic paralyses are a group of rare inherited disorders that cause temporary episodes of muscle weakness or paralysis. Periodic Paralysis is found in all races and in both sexes. Attacks can begin at any age. Some patients have their first attack within minutes of birth, but a few don't have symptoms until they are in their 60s or 70s. The paralysis can be mild, and confined to one limb, or so severe the patient cannot breathe on their own. Attacks can last only a few moments or go on for days, depending on the type of periodic paralysis the person has. Some forms of periodic paralysis include muscle stiffness or rigidity as part of the attacks. Some forms include permanent muscle weakness which happens over a period of many years.
How do you get periodic paralysis?
Most cases of periodic paralysis are inherited, but a family history may not always be obvious. Only one parent need carry the affected gene, and that parent need not show symptoms. About half of the females and a few men who carry the gene have no symptoms, or have such mild symptoms that they are never recognized as periodic paralysis. These people can still pass the gene on to their children. Each child of an affected parent has a 50% chance of inheriting the gene. There is no prenatal test available at this time and it is impossible to predict with any accuracy whether any given child will inherit the gene.
Genetic research has now revealed that periodic paralysis is caused by mutations in the genes that control the development of certain ion channels in the muscle membrane. Ion channels are openings that pierce the muscle membrane and act as gateways for the movement of ions in and out of the cell.
What determines which kind of periodic paralysis I have?
The ion channel which is affected determines the type of periodic paralysis. So far about 30 different mutations have been identified, all affecting either the sodium or calcium channels. DNA testing is available for a limited number of mutations, but cannot be relied on for diagnosis. Many patients who have clear family histories of periodic paralysis and have been diagnosed by time-honoured and medically accepted standards are still testing negative on commercially-available DNA tests. Commercial labs only test for the two or three most common gene mutations found in Hypokalemic Periodic Paralysis and one or two genes in Hyperkalemic Periodic Paralysis when more than 30 mutations have been identified. In addition there are mutations which have yet to be identified. This should make it obvious that a negative DNA test does not rule out a diagnosis of periodic paralysis.
How does a gene mutation cause episodic paralysis?
But how does a mutation in an ion channel cause temporary muscle paralysis? Because ions are charged. The movement of ions from one side of the muscle membrane to the other causes an electric current. When ions are separated from each other, negative from positive, across a barrier - the muscle cell membrane for example - they produce a voltage. In this case ions are used for electrical signaling.
For the muscles to work properly the ions must be kept in the correct ration inside and outside the cell. When the ion channels that control these exchanges are mutated they are prone to malfunction. In periodic paralysis the ion channels fail to regulate the flow of ions under certain conditions, and the electrical signals which keep the muscles moving come to a standstill.
How many types of periodic paralysis are there?
The periodic paralysis have historically been divided into types by how the patient reacts to potassium. In the most common form of periodic paralysis patients may experience paralysis or weakness after they eat sweet or starchy foods, and the weakness goes away when treated with potassium. This form is called ‘Hypokalemic Periodic Paralysis’. These patients experience a fall in potassium levels during weakness. The potassium may fall a lot or only a little. It may stay within normal levels but it does usually fall, even if by only .5 of a point. Until very recently all identified mutations associated with HypoKPP had been on the calcium channel, but recently a sodium-channel variant was discovered in one family.
There is a secondary type of HypoKPP which is associated with an overactive thyroid gland. This type of HypoKPP is called ‘Thyrotoxic HypoKPP’ (TPP). It is far more common in Asian males than in females (a ratio of 6 to 1) but can be found in people of all races and both sexes. When physicians say periodic paralysis is only found in Asian males this is the type of periodic paralysis they are thinking of. It isn't clear if there's a genetic component in Thyrotoxic Periodic Paralysis. No gene mutation has been found yet.
There is a rare form of periodic paralysis called Andersen's Syndrome. In this form, the potassium shifts during attacks of paralysis are inconsistent, and traditional classifications of Hypokalemic Periodic Paralysis or Hyperkalemic Periodic Paralysis cannot be applied. Patients may also have generalized weakness between attacks. In addition Andersen's Syndrome patients experience irregular heart rhythms including a prolonged QT interval. Some have unusual facial and hand characteristics, such as short stature, clinodactyly (an inward curvature of the 5th fingers), scoliosis, widely spaced eyes, low-set ears, a broad forehead and a poorly developed jaw. These signs may be absent or very subtle, or may exist in other family members who show no symptoms. Andersen's Syndrome is inherited in an autosomal dominant pattern. One gene mutation has been identified on the potassium channel.
An example of webbed toes sometimes seen in Andersen's Syndrome
Some patients develop paralysis or weakness (and sometimes muscle stiffness) when they eat potassium-rich food. People who develop weakness in response to potassium are said to have 'potassium sensitive' periodic paralysis. This is usually called Hyperkalemic Periodic Paralysis because most patients experience some elevation of blood potassium levels either during or between attacks of weakness. Doctors sometimes give patients a potassium solution to test for HyperKPP. This test is called a potassium challenge. HyperKPP is due to a mutation in the sodium channel.
There is another form of periodic paralysis called Normokalemic Periodic Paralysis. NormoKPP is fairly rare. People with NormoKPP do not experience any alteration of their blood potassium levels during weakness, but most experience weakness when challenged with potassium. DNA studies have revealed that at least some cases of NormoKPP are due to a mutation in the sodium channel and are a variant of HyperKPP. For now most physicians in the field consider NormoKPP and HyperKPP variations of the same disorder.
Paramyotonia Congenita (PMC) is a form of periodic paralysis which produces muscle stiffness or rigidity and weakness in response to cold or activity. PMC comes in potassium-sensitive and hypokalemic forms, but results from a mutation in the sodium channel. It can accompany other forms of Periodic Paralysis or it can occur alone. It seems to occur most often in combination with Hyperkalemic Periodic Paralysis.
Disclaimer
The information on this site is based on current medical knowledge but should never at any time be substituted for the advice and care of a properly qualified medical consultant. For medical advice seek the services of a physician.