Periodic Paralysis

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Periodic Paralysis In Focus Dear Readers Fast Facts This “In Focus” report is the third in a series of MDA’s three-year commitment for all Hypokalemic periodic paralysis MDA comprehensive reports about the latest in periodic paralysis research as of March Hypokalemic PP can begin anywhere from neuromuscular disease research and manage- 2009 is $1,938,367. The Association’s early childhood to the 30s, with periodic ment. allocation for research on hyperkalemic attacks of severe weakness lasting hours This report focuses on the periodic and hypokalemic periodic paralysis to days. The frequency of attacks gener- paralyses, a group of disorders that result from research since 1950 is $8,125,341. ally lessens in the 40s or 50s. Permanent malfunctions in so-called ion channels, micro- MDA’s allocation for the recently weakness may persist between attacks, scopic tunnels that make possible high-speed identified Andersen-Tawil syndrome usually beginning in middle age and pro- movement of electrically charged particles is $515,430 since 2001. MDA is cur- gressing slowly over years. across barriers inside cells and between cells rently funding 11 grants in the periodic The most common underlying cause and their surroundings. paralyses. is any of several genetic mutations in When ion channels fail to open or close The periodic paralyses are gener- a gene on chromosome 1 that carries according to an exquisitely fine-tuned program, ally divided into hyperkalemic periodic instructions for a calcium channel protein episodes of paralysis of the skeletal muscles paralysis, hypokalemic periodic paralysis in skeletal muscle fibers. When this chan- and even temporary irregularities in the heart- and Andersen-Tawil syndrome. The first nel fails to transmit a signal to a calcium beat can occur. two are caused by genetic defects in storage area inside the cell, the muscle Throughout history, and unfortunately high-speed tunnels in skeletal muscle fiber can’t contract. A minority of people down to the present day, people who experi- fibers known as ion channels. The last is have sodium channel mutations, but not ence episodes of paralysis or weakness, inter- due to such defects in both skeletal and the same ones that cause hyperkalemic spersed with periods of normal functioning, cardiac muscle. periodic paralysis. have been met with suspicion by their peers All forms of periodic paralysis affect and even their doctors. Individuals have been both sexes equally and are inherited in Andersen-Tawil syndrome accused of faking their attacks to gain atten- a dominant manner, meaning only one This syndrome usually begins in child- tion or shirk their responsibilities, and parents genetic flaw (mutation) from one parent hood or adolescence and is characterized have been suspected of child abuse when their can cause the disease. by episodes of weakness of the skeletal children displayed these mysterious symptoms. muscles and irregular heartbeat in the Today, molecular biology has pinpointed the Hyperkalemic periodic paralysis cardiac muscle. Occasionally people may precise mechanisms that underlie the periodic Hyperkalemic PP usually begins early develop permanent weakness between paralyses, and drug trials to treat them are in childhood, with episodes of muscle episodes. Heartbeat irregularities can under way. There is much work to be done, but weakness or paralysis lasting from 15 be serious enough to warrant treatment awareness of the diagnosis can provide signifi- minutes to hours or even days. With with medication or electronic devices. cant reassurance and help in managing these time, some people develop permanent Widely spaced eyes, low-set ears and a conditions. mild or moderate weakness that persists small chin also are characteristic of this This special section includes: between bouts of severe weakness. disorder. • “Fast Facts” about periodic paralysis Some patients also experience episodes The underlying cause of Andersen- • An update on state-of-the-art research and of myotonia, the inability to relax mus- Tawil syndrome is any of a number of disease management, with first-person cles completely. genetic mutations in a chromosome 17 stories from families affected by periodic The underlying cause is any of sev- gene for a potassium ion channel present paralysis eral genetic mutations in a gene on chro- in both skeletal and cardiac muscle tissue. • Information about genetic testing mosome 17 that carries instructions for When these channels fail to open, the To learn more about periodic paralysis, visit a sodium channel protein. The sodium exit of potassium from muscle cells after www.mda.org or call your local MDA office at channels in skeletal muscle can’t close they contract is impaired, and the cells (800) 572-1717. properly, permitting an excess of sodium can’t “reset” to receive further contraction ions to enter the muscle fibers. signals.

1 In Focus: Periodic Paralysis ©2009 MDA In Focus: It’s All in the Muscles, Not the Head Individuals and families struggle to manage the periodic paralyses, a group of diseases that’s too often misunderstood by teachers, employers and even health professionals by Margaret Wahl

People who know me know I lead an visited the MDA clinic at Yale University added to local extremely active life,” says Linda Feld in New Haven, Conn., where a doctor anesthetics, of Longwood, Fla. “People don’t see me suggested her condition might be peri- also can cause as somebody on a scooter. I’m Linda, odic paralysis but wasn’t sure. problems. If and I do all these things every day, and She tried to work, but soon “it the respiratory they know me for me. I tell people that became more and more difficult to hold muscles are periodic paralysis has become my friend. down a job. The weakness episodes affected, respi- It’s along for the ride, but it’s not going to would come on, and I couldn’t get out of ratory insuf- rule my life.” my desk chair at work. I’d be sitting there ficiency can Feld, now 59 and a hospice volunteer, working and couldn’t get up to go to the result. Linda Feld didn’t get a says her experience with the genetic copy machine. It became impossible to Feld’s father definitive diagnosis until she disease she now knows as hypokalemic hold a job.” became com- was 56 years old. (“low potassium”) periodic paralysis As she aged, the paralysis episodes pletely paralyzed after the anesthesia he goes back to her earliest memories, at ceased, but were replaced by progres- was given for the tracheostomy proce- age 3 or 4. sive and ultimately permanent weakness. dure and succumbed to a respiratory “I would develop a limp [periodical- (The lack of episodes and the permanent arrest a few days later. ly],” she recalls. “We’re talking the early weakness made diagnosis even more Feld finally got a definitive diagnosis 1950s, and not much was known about elusive.) She tried breeding dogs, but the when she was 56 years old, through the periodic paralysis. Even though my father work of maintaining a kennel eventually laboratory of Frank Lehmann-Horn at was disabled, he didn’t have a diagnosis.” proved too taxing. Ulm University in Germany. An orthopedic specialist suspected Feld’s sister, Sally, nine years younger, Lehmann-Horn, who received several her legs were of unequal length and pre- began following a similar pattern. “When MDA grants in the 1990s to study the scribed a lift for her shoe and supportive she reached her teenage years, she periodic paralyses, was originally trained footwear. “It was always very important started with terrible episodes of muscle as an engineer, later becoming a medical to my parents that I wore really sturdy cramping,” Feld recalls. Sally was given doctor. He’s widely regarded as an out- shoes. I wanted to be like the other kids an erroneous diagnosis of limb-girdle standing contributor to the study of ion and wear sneakers,” Feld says. muscular dystrophy. channel physiology, having done more to “I was never good at gym in school. Their father retired at age 55 because describe its behavior in health and dis- There was teasing by fellow classmates. of continued weakness, including weak- ease and to apply his findings to patient I couldn’t run fast. When I reached ness of his respiratory muscles. A bad care than perhaps any other professional. my teen years, I started having terrible chest infection when he was 72 caused Feld says the disease has forced many muscle cramps. There was nothing that his doctor to recommend a tracheostomy, compromises in her life. “I had to learn would alleviate the pain. The muscles a surgical opening in the trachea, through I could not be everything that every- became rock hard. It was not my whole which mucus would be suctioned out. body else was. I couldn’t be the athlete, body, always just a limb. Those cramps The family was unaware at the couldn’t follow the crowd and do what lasted 24 to 48 hours. Then they would time that certain anesthetics, both gas they did. I couldn’t go out and go drink- start to subside, but the weakness took and local, and muscle relaxants called ing with them. Alcohol was a big trigger. weeks to come back from. I missed big “depolarizing” agents, frequently used I wish I had known earlier in life some of segments of school.” during surgery, can cause long-lasting the things that work for people.” Feld finished high school and went on and severe weakness in people with Today, she manages her disease with to college. When she was about 20, she periodic paralysis. Epinephrine, often a medication called eplerenone (Inspra),

2 In Focus: Periodic Paralysis ©2009 MDA which keeps her serum potassium levels negative charge. PP are more likely to experience an attack up; potassium supplements as needed; Ions have a special role to play in skel- of paralysis when their serum potassium and avoidance of certain activities, foods etal and cardiac muscle cells, where their is temporarily high, and those with hypo- and medications. concentrations rapidly change in response kalemic PP are more likely to experience Carbohydrates and salt bother her, as to signals from nerve cells. These chang- one when their serum potassium is tem- does repetitive muscle activity, like peel- es, which allow muscles to contract and porarily low. (Normally, serum potassium ing potatoes. “I work with computers, relax, are made possible by the sensing levels are 3.5 to 5.0, measured in units and that doesn’t bother me,” she says. function and the extremely rapid opening called “milliequivalents” per liter.) “But if I were to hold a potato and use and closing of ion channels. Most people have ion channels that a peeler to keep peeling that potato, my work so effectively that they can quickly hand would become paralyzed.” Channel problems can readjust for a transiently high or low Being cold can trigger an attack, as cause myotonia, blood potassium level, so that muscles can corticosteroid medications (such as stay poised to receive nerve signals that prednisone). weakness or paralysis allow them to contract or relax. But in She’s undergone a hip fracture repair There are three major periodic paralyses: periodic paralysis, these ion channels, and a hysterectomy with spinal instead of hyperkalemic (high potassium) periodic because of a genetic mutation, don’t general anesthesia. “That was a piece of paralysis, hypokalemic (low potassium) work the way they should. They may the puzzle that was extremely important periodic paralysis, and Andersen-Tawil open or close too easily, or with difficulty; to get,” she says. “We have a very strict syndrome, explains Louis Ptacek, a neu- or they may stay open or closed too long. anesthesia protocol.” rologist who specializes in the study and Or they may fail to transmit a signal to “I’m happy to be the vehicle to tell the treatment of ion channel diseases at the another part of the cell. story to as many people as possible, so University of California at San Francisco. When serum potassium levels change that the children growing up today with The first two affect only the channels in response to dietary intake, medica- this disease do not have to follow the same in skeletal muscles. The last affects ion tions, cold temperatures, exercise, rest frustrating path I did,” Feld says. She wel- channels in both skeletal and cardiac or anesthesia, the channels can’t quickly comes inquiries about periodic paralysis, muscles. adjust to compensate for the change. especially the diagnosis odyssey, and can During the 1990s, when he was an Patients then become temporarily para- be reached at [email protected]. MDA research grantee at the University lyzed, although not necessarily through- of Utah, Ptacek played a major role in out the body. A more localized attack may Ion channels let muscle the identification of the genes underlying affect just part of the body, such as a leg fibers contract, relax hyper- and hypokalemic periodic paraly- or arm. sis. More recently, he’s received MDA In some cases people also experi- Periodic paralysis results from any of a support to study Andersen-Tawil syn- ence a tingling sensation. Pain or number of defects in microscopic tunnels drome at the University of California. prolonged contraction (myotonia), (channels) in muscle cells, also known as Although the first two periodic paraly- sometimes with severe cramping and muscle fibers. These channels allow elec- ses are named for their relationship to hardening of the muscles, is most likely trically charged particles to move in and serum potassium levels (kalium is Latin to occur in hyperkalemic PP. Permanent out of the cell in fractions of a second, or for potassium), this can be misleading, weakness between attacks sometimes in some cases to sense and propagate an Ptacek says. develops. electrical charge in a cell. (See, “How Ion People with periodic paralysis often Channels Regulate Muscle Contraction,” have normal serum potassium levels ‘Interesting and different’ pages 4-5.) when tested between attacks, and even Electrically charged particles of sodi- often during an attack, contributing to Andersen-Tawil syndrome is a more um, calcium, potassium and chloride are the difficulty of diagnosing their disease. dangerous condition than the other two known as “ions.” They’re normally kept “The term ‘kalemic’ has to do with the forms of PP because of its potential to within very narrow ranges of concentra- ability to precipitate attacks,” Ptacek says. induce serious abnormalities in heart tion inside cells, in the fluid surrounding “It does not have to do with whether rhythm. Ellen Andersen at the University cells and in the bloodstream. Sodium, serum potassium is high or low during Hospital of Copenhagen (Denmark) is calcium and potassium particles carry an attack.” credited with the first description of this positive charges, while chloride carries a In general, people with hyperkalemic disorder back in 1971.

acetylcholine nerve fiber muscle fiber

muscle fiber sodium acetylcholine ions receptor membrane sodium channel

Acetylcholine leaves the nerve fiber and docks on receptors in the muscle Sodium channels open in response to this small depolarization, permitting membrane, causing that area of the muscle fiber to become slightly more a huge flow of positively charged sodium ions to enter the muscle fiber. The positive (“depolarized”). depolarization is greatly amplified, and a brief electrical impulse (“action potential”) spreads throughout the fiber.

In the early 2000s, Rabi Tawil at the not on the X chromosome and that one environment, such as when foods high University of Rochester (N.Y.) led an defect, inherited from one parent, is suf- in potassium are ingested or when a effort to collect a large cohort of patients ficient to cause the disease. But in many person rests after exercising. Under these and refine the diagnostic criteria. Tawil cases, the person with periodic paralysis circumstances, the sodium channels fail is co-director of the MDA clinic at the knows of no family history of the condi- to close right away, allowing sodium to University of Rochester Medical Center, tion. In these cases, it’s believed to be continue leaking into the muscle fiber and where he conducted MDA-supported caused by a new genetic mutation, not keeping the muscle fiber (muscle cell) research on what would later become one that’s been seen before in the family. membrane depolarized. known as Andersen-Tawil syndrome. (From that point on, however, it can be This depolarization may cause pro- Ptacek and colleagues identified the inherited by future generations.) longed muscle contraction temporarily. underlying genetic and biochemical However, weakness or paralysis soon mechanisms. A long and winding occur, because a depolarized muscle fiber “Andersen-Tawil syndrome is inter- road led to hyperkalemic can’t receive new signals from a nerve esting and different,” Ptacek says. “It’s cell. a complicated, multisystem disease. periodic paralysis “Too much potassium narrows the Like other periodic paralyses, it’s highly diagnosis penetrant, which means that if you have Hyperkalemic PP stems from mutations the genetic mutation, you get the dis- in the sodium channels that sit on the ease. But the variability of the disease is surface of muscle fiber membranes. extremely high. It’s very different from These channels normally respond to one patient to another, even within the a signal from a nerve cell by opening same family.” briefly and allowing sodium ions to flow Although doctors and patients have into the fiber. long noted that periodic paralysis could Sodium ions carry a positive electrical run in families, scientists did not begin to charge, and when they enter a cell, they identify the precise genetic abnormalities make it more positive, a phenomenon involved until the 1990s. referred to as “depolarization.” All forms of periodic paralysis are But mutations in the sodium channel Before her periodic paralysis was diagnosed, the parents of Faith Couture (in front) were told their inherited in an autosomal dominant fash- gene cause these channels to malfunc- daughter might have seizures, growing pains, arthritis ion, which means the genetic defects are tion when they’re in a high-potassium or multiple sclerosis.

chloride ions potassium potassium channel ions

calcium channel calcium ions cholride channel

thick filament

thin filament

Depolarization of the muscle fiber is sensed by calcium channels and trig- The sodium channels spontaneously close, potassium channels open, and pos- gers the release of calcium ions from internal storage areas. This flood of itively charged potassium ions exit the fiber. Chloride channels also stay open, released internal calcium is the chemical signal that causes the thick and and negatively charged chloride ions enter the fiber. All these actions cause thin filaments of the muscle fiber to slide past each another (contract). the inside of the fiber to become more negative (“repolarized”). The muscle fiber returns to its resting state, calcium is pumped back into the internal storage vesicles, and the fiber is now ready to accept another surge of positively charged ions in response to stimulation from a nerve fiber. (When several muscle fibers are at rest, a muscle can relax.)

safety margin, and people with hyper- “It’s in your daughter’s head. Get over it.” Faith is in the extremely unusual situ- kalemic periodic paralysis have less of Faith’s father was in the Air Force at ation of being steered away from most a safety margin to begin with,” Ptacek the time, and the frequent moves around fruits and vegetables, which are high in says. “When you increase the extracel- the country added complications to the potassium, and toward sugar, which can lular potassium, it pushes them over a diagnostic process. ward off an attack of paralysis. “For now threshold where the cell remains depo- “We’ve had so many misdiagnoses we try to manage her diet and watch how larized.” that if we hadn’t taken the initiative and much she has in fruits and vegetables,” That’s what began happening to Faith been guided by two or three doctors, we her mother says. “The only problem Couture of Dayton, Ohio, when she was 2 probably would have gone with whatever we have with her is tomatoes. She’s a years old. She’s now 9. we heard. We were told 19 times this was Southern child and loves tomatoes.” “It looked like she would play pos- seizures.” Because some kidney diseases sum when anybody would get her out of When Faith was 7, the family received require a potassium-restricted diet, a the car,” says her mother, Enola. “But we orders to go to Ohio and ended up at good reference for the potassium content started thinking, ‘she’s too young to do Children’s Hospital in Dayton. There, a of foods, and a method to reduce the that.’ We watched how she reacted when geneticist who had worked with Robert potassium in vegetables, is the National we set her on the ground. She was like a Griggs, a longtime MDA grantee at the Kidney Foundation Web site at www. blob of Jello. She would just collapse and University of Rochester, thought he knew kidney.org. (There are, however, marked start crying.” what the problem was and recommended differences between the management of Soon after the car episodes, Faith DNA testing. kidney disease and periodic paralysis, began waking up from naps unable to “They took her blood two days before even if they overlap in one area.) The move, sweating and screaming. There her eighth birthday,” Enola recalls. “When potassium fact sheet can be found at was no family history of anything like it came back a month later, it was like www.kidney.org/news/newsroom/fs_new/ what Faith was experiencing. Christmas.” The diagnosis — hyperkale- potassiumCKD.cfm; or you can contact The pediatrician suggested the prob- mic periodic paralysis — “wasn’t some- the Foundation at (800) 622-9010. lem was “growing pains,” later revising thing we were extremely excited about,” Giving Faith some sugar to take to his diagnoses to juvenile arthritis or mul- Enola says, “but we were excited to know school has helped somewhat as well, tiple sclerosis. A referral to one neurolo- that we weren’t crazy.” says Enola. A Coke around 11 a.m. gist resulted in a diagnosis of learning Faith’s episodes still aren’t well con- seems to have helped a little bit. “She’s disability and speech impairment, while trolled, but her mother says they’re “still not having [attacks] as frequently. We another neurologist told the Coutures, testing everything.” keep an eye on her.”

5 In Focus: Periodic Paralysis ©2009 MDA Father, son and his children also are affected has been “As a kid, I was very clumsy, but daughter struggle with even harder than having the disease we didn’t really know why,” he recalls. himself. In 1972, when he was 6 years old, he hypokalemic PP Parker’s parents knew something was underwent a muscle biopsy at Children’s Carl Parker, 43, of Enon, Ohio, who has wrong fairly early, but they didn’t know Hospital in Columbus, Ohio (now hypokalemic periodic paralysis, says his what. As in Faith Couture’s family, no one Nationwide Children’s). Neurologist life has never been easy. But finding out else was affected. Jerry Mendell, then a young physician

The Periodic Paralyses Disorder Hyperkalemic Periodic Paralysis Hypokalemic Periodic Paralysis Andersen-Tawil Syndrome Location of problem sodium channel calcium channel (most common) potassium channel sodium channel Location of gene chromosome 17 chromosome 1 chromosome 17 chromosome 17 Inheritance pattern dominant dominant dominant Functional defect channel does not close properly; calcium channel on cell surface channel does not open properly; prolonged sodium leak into cell does not transmit signal for inte- potassium can’t leave cell rior calcium release Average age of onset before age 10 age 5 to 35 age 2 to 18 Average duration 30 minutes to 4 hours 2 to 24 hours 1 to 36 hours of episodes Maximum weakness mild to severe severe moderate Development of may occur; increases with age may occur; increases with age may occur; increases with age permanent weakness Muscle pain may occur in exercised muscles may occur in exercised muscles may occur in exercised muscles Episode triggers high blood potassium; high low blood potassium; high car- high or low blood potassium, potassium intake; fasting; cold bohydrate intake; rest after exer- depending on exact genetic temperatures; certain anesthetics; cise; cold temperatures; certain mutation; certain anesthetics; depolarizing muscle relaxants anesthetics; depolarizing muscle depolarizing muscle relaxants; relaxants other triggers consistent with either hyper- or hypokalemic PP Treatment • hydrochlorothiazide, furosemide, • potassium supplements, • cardiac medications such as acetazolamide or dichlorphen- acetazolamide (can harm some beta blockers and anti-arrhyth- amide; glucose-insulin solution; patients), dichlorphenamide, mics, implanted pacemaker- inhaled albuterol; drugs that bind spironolactone or eplerenone defibrillator potassium • high-potassium, low-carbohy- • acetazolamide or dichlorphen- • carbohydrate intake, low-potas- drate, low-sodium diet; warmth; amide can help or harm sium diet keep moving • high- or low-potassium diet, • frequent meals, warmth, keep • avoid certain anesthetics and depending on mutation moving depolarizing muscle relaxants • avoid certain anesthetics and • avoid certain anesthetics and depolarizing muscle relaxants depolarizing muscle relaxants

6 In Focus: Periodic Paralysis ©2009 MDA and now a longtime MDA research diagnosis, it triggers a paraly- grantee at Ohio State University and sis attack by lowering serum Nationwide Children’s, arranged for a potassium. muscle biopsy. The diagnosis came back “Potassium travels into “unknown,” Parker says, but the tissue muscle cells when glucose appeared to have bubbles called vacu- goes in,” Ptacek says. “If oles. “They said it looked like a Milky you drop a hypokalemic peri- Way candy bar,” he says. odic paralysis patient’s serum As his childhood progressed, Parker potassium level, you can pre- continued to be clumsy. “Some days I cipitate an attack.” didn’t function well. I had trouble get- “It was the worst spell I Cory Parker (left) had his first periodic paralysis episode at age 8, ting up and down, couldn’t run well and ever had,” Parker says. “They while his sister, Brittany (right), didn’t have hers until age 19. would fall down for no apparent reason. had pulled the door shut on my room that sodium and by cold temperatures. They tried high-top shoes. We went to night. I was trying to yell, but I couldn’t, “Until about 25, it was very rough. I different doctors, but they didn’t under- and I couldn’t reach the buzzer.” had a lot of attacks. I always had a rough stand the problem.” Parker was finally taken to Ohio State time holding jobs. It’s hard to explain to Then, at age 12, Parker experienced by ambulance, where they started treating people. I’m 6 feet 2, 290 pounds. I could his first true attack of periodic paralysis. him with oral potassium. Several hours tear the barn doors off a barn, but some “My parents were out for the evening,” later, his serum potassium level was back days I can’t get out of bed.” he remembers. “I was sitting on the up, and the diagnosis became clear. Parker has the type of hypokalemic couch, eating popcorn and drinking a “They did a lot of tests. They finally PP caused by a mutation in a cell-sur- pop. I went to get up and I couldn’t.” got me medicated and got me going.” face calcium channel gene. (A minority Parker’s parents arrived home, and his Parker began taking oral potassium and of patients have hypokalemic PP caused father tried unsuccessfully to get him up acetazolamide. by sodium channel mutations that are and walking. “My legs didn’t work, and my Ptacek admits that the mechanism by different from those that cause hyperka- arms were weak. I could still move them a which acetazolamide and other diuret- lemic PP.) little bit. I could wrap my arms around my ics in the “carbonic anhydrase inhibitor” The surface calcium channels, unlike dad’s neck,” he remembers. family actually work in periodic paralysis the other ion channels, don’t play an At Children’s Hospital, Parker’s serum remains uncertain. Some experts believe important role in the movement of calcium potassium level was 1.8, which is very they interact directly with ion channels, into and out of the muscle fiber. Instead, low, and he was started on potassium he says, while others believe their effects their role is to sense changes in the supplements. “That started a whole pro- on the acidity of the serum are involved. electrical state (voltage) in the fiber and cess of doctoring. We went through a “The teenage years were very rough transmit signals to storage areas inside whole gamut of potassium [types] to find for me,” Parker says. He had paralysis the fiber, from which calcium ions are then the one that worked for me.” Although attacks every few days, often requiring a released, causing contraction of the fiber. Parker still didn’t have a diagnosis, at hospital stay. When the surface calcium channels least he had something that seemed Like other periodic paralysis patients, malfunction in hypokalemic PP, this sig- treatable, if imperfectly. he soon learned that high-carbohydrate naling doesn’t happen, and the muscle Then, at 15, he experienced a major meals (such as the popcorn and soda he fiber doesn’t contract. attack of paralysis. He was already in the ingested the night of his first full-blown In 2002, Parker’s DNA was tested at local hospital undergoing intravenous episode) trigger attacks. (Like intrave- Lehmann-Horn’s laboratory in Germany, treatment for an extremely low serum nous glucose, these carbohydrates cause the same lab that would later pinpoint potassium level. Unfortunately, in addi- potassium to migrate from the serum Linda Feld’s genetic abnormality, and he tion to potassium, the IV contained into the cells, lowering serum potassium learned the precise mutation that affects glucose (sugar), which drives potassium levels.) But the paralysis was still unpre- his calcium channel gene. from the bloodstream into cells. dictable. Although his own attacks of paralysis When treating potassium deficiency in “I could eat almost anything and not have become less frequent, he now has a other conditions, that would be the goal. have an attack and then three days later son and a daughter with the disease. But in hypokalemic periodic paralysis, have an attack,” he says. He also found “From what we were told [in the which Parker would soon learn was his attacks could be triggered by excess 1980s], we thought it couldn’t be geneti-

7 In Focus: Periodic Paralysis ©2009 MDA cally transferred,” Parker says. He and his Laboratory Directory and search by dis- the kidneys but maintains or raises wife, Rhonda, had a daughter, Brittany, in ease name.) serum potassium levels. She also takes 1989, and a son, Cory, in 1991. Frank Lehmann-Horn and Karin acetazolamide, although she’s reduced Cory had his first paralysis episode Jurkat-Rott conduct extensive genetic her dosage of that drug, and potassium at the age of 8. Before then, nothing testing for all three types of PP (including supplements. unusual had been noted. “We never saw Andersen-Tawil syndrome). Their labora- “I also learned that potassium is a any signs with Cory, growing up. He was tory is at Ulm University in Germany, but really good friend of mine,” Feld says, never clumsy. He played soccer. Then they also help U.S. patients. The Web “and that taking a lot of potassium is not a this one day he had a bad attack.” address, with all pertinent information, is dangerous thing for somebody with hypo- Now 18, Cory manages his episodes http://physiologie.uni-ulm.de/ kalemia. If I feel an arm muscle getting with potassium supplements and acet- angewandte-physiologie. Contact stiff, I take potassium and get rid of it.” azolamide, as does Carl. And, like his Lehmann-Horn at frank.lehmann-horn@ father, he finds high-carbohydrate or uni-ulm.de. MDA supports basic and high-sodium meals, especially late at “I traveled throughout the United clinical research night, must be avoided. A late-night taco States trying to find a diagnosis,” says and milkshake will almost invariably Linda Feld. “I feel the [doctors] in the Today, MDA is allocating about $2 million cause paralysis. Resting after exercise United States try to put people with for studies related to periodic paralysis. also can trigger an attack. periodic paralysis into too tiny a box. Of immediate relevance to patients and “He struggles as a young man, going They have a very definite diagnosis in families is a multicenter clinical trial to high school,” Carl says. “The teenager their mind. They describe the disease in comparing acetazolamide with another years are hard with this disorder. Usually very narrow terms, so it’s hard to fit the carbonic anhydrase inhibitor called he gets to school regularly. He goes in box they’re trying to put you into. Dr. dichlorphenamide for people with hyper- late two or three times a week. Usually Lehmann-Horn goes to the nth degree. or hypokalemic periodic paralysis. he’ll be weak from the waist down, some- He makes a box for the patient. If he For more about this study, which is times arms or legs, sometimes both. For doesn’t find your mutation, he does link- being funded by the National Institutes of him and me both, it can be just one leg, age analysis on the whole family.” Health with additional support from MDA, both legs, one arm or full body. You just Linkage analysis is a technique in contact project coordinator Patty Smith at never know what it’s going to be.” which the DNA of family members with the University of Rochester (N.Y.) Medical And then came another blow. In and without a genetic disorder is com- Center, (585) 275-4339 or patty_smith@ January, Brittany, who had just turned 19, pared in an effort to find the disease- urmc.rochester.edu. had her first paralysis attack. “Brittany associated difference. Other MDA-supported researchers never showed anything,” says her father. A study of Feld’s family revealed they are studying how mutations in genes for “She could run all day. She ran cross- had a previously unknown mutation in ion channels affect channel function and country, played basketball and all kinds of the gene for the voltage-sensing calcium muscle contraction; creating mouse mod- sports. It was a very hard pill to swallow.” channel. els of the periodic paralyses; and identify- Since then, she’s had some localized “I could never get a firm diagnosis ing the characteristics of Andersen-Tawil attacks, in an arm or leg or foot, but no from any physician until I was genetically syndrome. full-fledged episodes. She has potassium identified by Dr. Lehmann-Horn in the fall For updated information about clinical supplements to use if needed, but, Carl of 2006 at age 56,” Feld says. “It was my trials and studies in the periodic paraly- says, they’re taking a wait-and-see atti- new birthday. My diagnosis up to that ses, see the clinical trials section of the tude to see what her treatment will be. point had included and excluded periodic MDA Web site at www.mda.org/research/ paralysis several times, as well as many ctrials.aspx and the National Institutes of Genetic testing can other diseases. Health clinical trials site at www.clinical- bring relief, assist with “Finding the mutation has made a trials.gov. q huge difference in my life, because they management were able to tell me what kind of drugs I Editor’s note: As this article went to Many laboratories in the United States could use to better manage the disease.” press, we learned that Carl Parker died and Europe now conduct genetic test- Feld now takes eplerenone (Inspra), a abruptly following an appendectomy. ing for the periodic paralyses. See so-called potassium-sparing diuretic, a The cause of death has not yet been www.genetests.org for a list. (Click on drug that increases water loss through determined.