What is Hypokalemic Periodic Paralysis?
Hypokalemic Periodic Paralysis (HypoKPP) is a rare inherited muscle disorder which is estimated to occur in only one of 100,000 individuals. Because it is inherited there may be several members in a single family who have the disorder, which makes it obvious that the one in 100,000 figure is a statistical average, and does not represent real patients.
Hypokalemic periodic paralysis causes attacks of muscle weakness or paralysis when the level of potassium in the blood drops. During severe attacks the patient may be unable to move and even appear unconscious. Even during paralysis the patient is awake and completely aware of their surroundings.
A very few patients with HypoKPP begin having having attacks in infancy but most have their first attack between the age of 10-14 years. About 65% of patients have an attack before they are 16, but some patients don’t have attacks until they are older. Patients who develop symptoms at a young age may only have an attack once in a while to begin with, but attacks tend to come more often later, and may eventually occur daily.
Attacks may last an hour or two or (sometimes) a day or two. Attacks vary from mild weakness in a hand, foot or limbs one time to complete paralysis the next. Some attacks cause muscle tenderness and aching and some are painless. Patients may also have abortive attacks – daily weakness which varies hour to hour or day to day. These attacks can last for months and may be mistaken for permanent weakness.
Abortive attacks become more common in patients as they enter their 40’s. Some patients quit having paralysis when they are in their 40’s and have abortive attacks instead. Abortive attacks can be more trouble than paralytic attacks, because young patients usually feel strong between attacks of paralysis and patients with abortive attacks rarely feel strong.
Weakness most often affects the muscles of the shoulders and upper arms and legs but may cause weakness of the the trunk/back muscles as well. A few patients have trouble breathing and swallowing during attacks. The low potassium level during attacks may cause irregular or weak heartbeat. Most patients have good muscle strength between attacks, but in most patients muscle tissue is damaged over time. Most patients have some reduction of muscle strength by the time they are 50-60 years old.
There is also a myopathic form of HypoKPP (myopathy = muscle weakness due to dysfunction of muscle fiber). Patients may be unaware of attacks of weakness or paralysis but as they enter their 30’s they begin to develop exercise intolerance, especially in the legs. By the time they are in their 60s they develop a permanent weakness of the legs which prevents them from climbing stairs, walking over rough ground, or walking distances. This weakness may make it necessary to use a wheelchair.
Why do I get weak during episodes?
During attacks of muscle weakness, potassium moves from the blood into muscle cells. This makes the cell unable to contract properly.
What tests are used to diagnose periodic paralysis?
A variety of tests are used. If the patient is brought to the hospital in the early stages of an attack it is easier for the doctor to do tests, but this rarely happens. If the paralyzed patient has a low level of potassium in the blood (3.0 or lower), and the weakness responds to potassium, it’s possible to test the urine to see if the patient is losing potassium in the urine. The patient with HypoKPP does not lose potassium in the urine during attacks. Diagnosis is not usually this easy, because the patient doesn’t have an attack when the doctor or hospital is handy, or the doctor doesn’t know which tests to do. There is more information on this website about diagnostic tests and techniques. See Diagnosis in Hypokalemic Periodic Paralysis.
What causes HypoKPP?
Hypokalemic Periodic Paralysis is caused by a genetic mutation which causes a malfunction in certain ion channels in the muscle membrane. Ion channels are tiny pores (openings) that allow ions (molecules) of sodium and potassium to move through the cell membrane. For the muscles to work properly sodium and potassium ions must be kept in the correct ratio inside and outside the cell. When the level of potassium in the blood falls these ion channels fail to regulate the flow of ions properly. The ratio 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. is paralysed. This person with HypoKPP is very sensitive to drops in serum potassium. Some patients with HypoKPP may become paralyzed while their potassium levels remain within “normal” limits.
No one else in my family has this disease. How did I get it?
HypoKPP is inherited in about two of three patients, but not everyone with HypoKPP has obvious symptoms. Some people have symptoms so mild they are passed off as “tired blood” or “chronic fatigue”, even laziness. So a parent may be affected without it being obvious. About one in three cases happen as a result of a mutation which takes place at conception, like any birth defect.
Will I pass this on to my children?
Any child of an affected person has a 50% chance of inheriting HypoKPP, but not all who inherit HypoKPP will have symptoms. In the same family one child may have mild symptoms, the next may have worse symptoms and others may be unaffected. Even identical twins may be affected to different degrees.
My potassium level is always in the normal range during attacks. Why call it Hypokalemic Periodic Paralysis?
Those with HypoKPP have attacks when the potassium falls. In many patients the potassium level drops well below normal, but some patients never have very low potassium. However the level of potassium always falls. Sweets or starchy foods trigger attacks because these foods cause potassium to move into the muscle cell, and lower the level of potassium in the blood. Potassium (by mouth or by an IV line) makes the attack go away. Patients with NormoKPP usually have an attack of weakness when they eat potassium-rich foods or are given potassium. Genetic tests show that ‘NormoKPP’ is a variant of Hyperkalemic Periodic Paralysis.
What triggers attacks?
Many HypoKPP attacks are triggered by food. Food triggers include sweet or starchy foods like candy, cakes, pie and other desserts, soft drinks which are sweetened with sugar, fruit juices, bread, cereal products, rice, potatoes, and pasta. Foods like these are digested very quickly and raise blood sugar rapidly. The pancreas responds to this rapid rise in blood sugar by producing a lot of insulin. Insulin drives potassium from the blood into the muscle cell, which triggers weakness. Salty foods, like potato chips or pickles, are also a trigger for many HypoKPP patients.
Getting too hungry, or eating a large meal (especially if you are very hungry) triggers episodes in many patients. Other common triggers include unusual activity or exercise – usually the day before the attack, but sitting still for too long may also trigger attacks.
Patients learn that pacing their activities is absolutely vital. The activity level should be kept close to the same each day. Sleep is a strong trigger. Many patients wake up paralyzed in the morning or after a nap. Getting too cold (or too hot) makes some patients weak. Humid weather or a rapid change in the weather (like a storm) can trigger attacks in some patients.
Some medications may cause attacks. These include muscle relaxants and beta-blockers, some tranquilizers, pain killers, antihistamines, the puffers used to treat asthma attacks, some antibiotics and cough syrups. The eye drops used to dilate the pupil during eye exams have been reported to cause paralysis. Epinephrine or adrenaline , a drug routinely added to local anesthetics, should be absolutely avoided by patients with HypoKPP. Many patients report paralysis attacks occurring in the dentist’s chair or following dental work, or after having a wound stitched or a mole removed. Over the counter drugs can be dangerous and should be avoided if at all possible. If it’s necessary to take something it’s wise to try 1/4 of the recommended dose to make sure it doesn’t cause weakness.
How do I avoid having attacks?
Learn what your triggers are and learn to avoid them. For some people this is enough. For others it is necessary to take daily medication.
Where is the best place for treatment of HypoKPP?
The best place for treatment is almost always the patient’s own family physician, if that physician is willing to read about HypoKPP and learn how to manage it. Every patient responds a bit differently to treatment. Patients are often best cared for by the doctor who cares for their overall health. A common illness like a 24-hour stomach flu can turn into a life-threatening emergency for a HypoKPP patient, and in these cases there is no time or opportunity to go to a far away specialist.
Who is doing research on HypoKPP?
There are a number of research teams working on the PPs. Research is concentrating on the genetics and mechanics of the channelopathies, rather than on therapy and management. There’s been nothing new in the way of therapy for many years, although we have learned how to apply therapies much more effectively, and we’ve made great strides in management.
Can I have a DNA test for HypoKPP?
Genetic testing is available, but it is not yet reliable enough to diagnose all HypoKPP patients. While a genetic test may be able to say you have HypoKPP, if the results of the test are negative that does NOT mean you do not have the disorder, as there are a number of variants which have yet to be identified. If you plan to be tested it is wise to talk about this issue with your physician ahead of time, just in case your test comes back negative (as many are still doing at this point). Make certain you will not be denied therapy by your physician or HMO should the test be negative!
Can HypoKPP be cured?
HypoKPP is caused by a mistake in the genetic ‘blueprint’ which was determined at the moment of conception. At present there is no cure. A person who has HypoKPP will have the disorder all their life, but there is treatment available.
What medications are prescribed for HypoKPP?
The carbonic anhydrase inhibitor acetazolomide (Diamox) is often prescribed for HypoKPP patients. This medication helps keep the potassium from getting out of balance in the first place, by affecting the mechanism that moves potassium from the blood into the cell. Other carbonic anhydrase inhibitors called dichlorphenamide (Keveyis) and methazolamide (Neptazane) are more potent, and often work on patients who have been on acetazolomide for many years and have become resistant to its effects. About 25% of patients do not respond to acetazolomide and must be put on other drugs. Patients who take carbonic anhydrase inhibitors must be alert to potentially dangerous drug interactions as they slow the excretion of other drugs from the system. Avoid large doses of aspirin when taking carbonic anhydrase inhibitors. Acetazolomide (Diamox) should be started at a low dose which is gradually increased to avoid uncomfortable side effects.
Diuretics which cause the kidneys to ‘spare’ (or conserve) potassium are also used to treat HypoKPP. Dyrenium and Aldactone (spironolactone) are in this family. Dyrenium is particularly useful as it causes the patient to excrete sodium as well as retain potassium. Dyrenium sometimes comes mixed with an agent which makes patients excrete potassium, so it’s important to make certain the medication the HypoKPP patient is receiving contains no potassium-wasting diuretic. Patients who are taking diuretics which cause the kidneys to conserve potassium should consult with their doctors before taking potassium supplements.
Most people with HypoKPP still require potassium, even on diuretic therapy, but it should be carefully monitored. Those on carbonic anhydrase inhibitors generally need to take some potassium to replace what is lost due to therapy itself. Most patients with HypoKPP use potassium to abort developing episodes. Patients differ in their reactions to different forms of potassium but, as a rule, most people find that the effervescent potassium citrate or bicarbonate tablets which dissolve in water are easier on the stomach. Potassium chloride tablets are slow to dissolve and are hard on most people’s stomachs, though some forms of potassium chloride capsules have coated granules of potassium which dissolve in the intestine and are much easier on the digestive system. If potassium chloride tablets are required these are preferred by many patients.
Will I be able to lead a normal life?
Most people with HypoKPP lead reasonably normal lives. Many cases of HypoKPP are mild, and even in those with severe and frequent episodes, medication and attention to diet and lifestyle issues can ease symptoms. There is no denying that more severely affected patients lead physically-compromised lives, especially patients with a long history of episodes. But less-affected patients are often able to be quite active, and some engage in fairly strenuous sports. Members of our HKPP Listserv group come from all professions and walks of life including physicians, nurses, teachers, lawyers, musicians, engineers, journalists, farmers and ranchers, a plantation owner, homemakers, accountants, and computer specialists.
Will I end up in a wheelchair?
This is a hard question to answer. Permanent muscle weakness is a fact of life for many older patients, and activities like climbing stairs and walking long distances may become very tiring, or even impossible. Many of our older members (65+) use a wheelchair or ‘scooter’ for distances outside the home, but walk inside the house. Very few rely on a wheelchair full time unless their condition is complicated by other problems.
Does HypoKPP affect the mind? Will my life be cut short by HypoKPP?
Several of our families have affected members who have lived well into their 80s, in complete control of their mental faculties. We have HKPP List members who are in their 80s who participate in discussions and are living in their own homes, even serving as caregivers to other family members. We have lost family members and loved ones to HypoKPP. In some cases this has been the patient’s decision, in others death was caused by a complication or medical mismanagement in which their HypoKPP played a part. In no case have we lost a patient in recent years to a paralytic episode.
reviewed and edited 17 October 2020