What is Periodic Paralysis?
Submitted by ian on Tue, 06/21/2011 – 22:55
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. Some patients have their first attack within minutes of birth, but a few don’t have symptoms until they are in their 60’s or 70’s. 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 develops over a period of many years.
How do you get periodic paralysis?
Periodic paralysis is caused by mutations in the genes that control the development and function 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. Most cases of periodic paralysis are inherited, but a family history may not be obvious. Only one parent need carry the mutated gene, and that parent may not show symptoms. About half of the females and a few men who carry the gene mutation have no symptoms or have such mild symptoms that they are never diagnosed 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 mutation. There is no prenatal test available at this time and it is impossible to predict with certainty whether any given child will inherit the gene.
What determines which kind of periodic paralysis I have?
The ion channel which is affected determines the type of periodic paralysis. As of April 2018, about 50 different mutations have been identified, affecting sodium, calcium or potassium channels. However, DNA testing still cannot be relied on for diagnosis. At least 20% of clinically diagnosed patients have mutations which have not yet been identified. A negative DNA test does not rule out a diagnosis of periodic paralysis.
How does a gene mutation cause episodic paralysis?
The movement of sodium and potassium ions from one side of the muscle membrane to the other creates an electrical current. For the muscles to work properly these ions must be kept in the correct ratio both inside and outside the cell. In periodic paralysis the ion channels fail to regulate the flow of ions properly when potassium levels in the blood fluctuate. The ratios of sodium and potassium inside and outside the cell become unbalanced. The muscle responds less when asked to move, which is felt as weakness. If the imbalance becomes pronounced the muscle quits responding at all, i.e., becomes paralyzed.
How many types of periodic paralysis are there?
The Periodic Paralyses include Hypokalemic PP, Thyrotoxic PP, Hyperkalemic PP, Paramyotonia Congenita von Eulenburg, the Potassium Aggravated Myotonias and Andersen-Tawil Syndrome.
What is Periodic Paralysis?
Submitted by ian on Tue, 06/21/2011 – 22:55
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. Some patients have their first attack within minutes of birth, but a few don’t have symptoms until they are in their 60’s or 70’s. 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 develops over a period of many years.
How do you get periodic paralysis?
Periodic paralysis is caused by mutations in the genes that control the development and function 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. Most cases of periodic paralysis are inherited, but a family history may not be obvious. Only one parent need carry the mutated gene, and that parent may not show symptoms. About half of the females and a few men who carry the gene mutation have no symptoms, or have such mild symptoms that they are never diagnosed 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 mutation. There is no prenatal test available at this time and it is impossible to predict with certainty whether any given child will inherit the gene.
What determines which kind of periodic paralysis I have?
The ion channel which is affected determines the type of periodic paralysis. As of April 2018 about 50 different mutations have been identified, affecting sodium, calcium or potassium channels. However DNA testing still cannot be relied on for diagnosis. At least 20% of clinically diagnosed patients have mutations which have not yet been identified. A negative DNA test does not rule out a diagnosis of periodic paralysis.
How does a gene mutation cause episodic paralysis?
The movement of sodium and potassium ions from one side of the muscle membrane to the other creates an electrical current. For the muscles to work properly these ions must be kept in the correct ratio both inside and outside the cell. In periodic paralysis the ion channels fail to regulate the flow of ions properly when potassium levels in the blood fluctuate. The ratios of sodium and potassium inside and outside the cell become unbalanced. The muscle responds less when asked to move, which is felt as weakness. If the imbalance becomes pronounced the muscle quits responding at all, i.e. becomes paralysed.
How many types of periodic paralysis are there?
The Periodic Paralyses include Hypokalemic PP, Thyrotoxic PP, Hyperkalemic PP, Paramyotonia Congenita von Eulenburg, the Potassium Aggravated Myotonias and Andersen-Tawil Syndrome.
Hypokalemic Periodic Paralysis
The periodic paralysis are loosely divided into types by how the patient reacts to potassium. In the most common form patients grow weak or paralyzed after foods or events which lower the level of potassium in the blood. Strength improves when the patient is given potassium. This form is called Hypokalemic Periodic Paralysis (HypoKPP). Attacks last from hours to days, and range from mild weakness to profound paralysis. Mutations associated with HypoKPP are on the calcium and sodium channels. MORE
Thyrotoxic Periodic Paralysis
The second type of HypoKPP 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 how much of a genetic component there is in Thyrotoxic Periodic Paralysis, but recently a potassium channel gene mutation was discovered in some patients with TPP. MORE
Hyperkalemic Periodic Paralysis
Patients with Hyperkalemic PP (HyperKPP) develop paralysis or weakness (and sometimes muscle stiffness) when they eat potassium-rich food. This is also referred to as ‘potassium sensitive’ periodic paralysis. This is usually called Hyperkalemic Periodic Paralysis because most patients’ potassium levels rise during attacks. HyperKPP is due to a mutation in the sodium channel. MORE
Normokalemic Periodic Paralysis
There is a variant form of HyperKPP called Normokalemic Periodic Paralysis. People with NormoKPP do not experience any change in their potassium levels during weakness, but most grow weak when given potassium. Genetic studies show that NormoKPP is due to a mutation in the same sodium channel as HyperKPP. Most physicians consider NormoKPP and HyperKPP variations of the same disorder. MORE
Paramyotonia Congenita
Paramyotonia Congenita von Eulenburg (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. MORE
Potassium Aggravated Myotonias
The Potassium Aggravated Myotonias (PAMs) in which potassium intake triggers an attack of muscle stiffness. These include Myotonia Fluctuans, which includes short attacks of varying degrees of mild muscle stiffness brought on by exercise, Myotonia Permanens, which causes severe and constant muscle stiffness which is made worse by eating potassium-rich food and exercise and Acetazolamide-responsive Myotonia Congenita, which causes painful myotonia. The muscles appear very well-developed in Acetazolamide-responsive Myotonia Congenita. The PAMs do not cause muscle weakness. MORE
Andersen-Tawil Syndrome
In Andersen-Tawil Syndrome (ATS) 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 ATS 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 small jaw. These signs may be absent or very subtle, or may exist in other family members who do not experience paralysis. Andersen-Tawil Syndrome is inherited in an autosomal dominant pattern. ATS mutations identified so far have been on the potassium channel. MORE