Hypokalemic periodic paralysis: Difference between revisions

Mutations altering the usual structure and function of these channels therefore disruptsdisrupt regulation of muscle contraction, leading to episodes of severe muscle weakness or paralysis. Mutations have been identified in [[arginine]] residues making up the [[voltage sensor]] of Na_v1.4. This voltage sensor comprises the S4 [[alpha helix]] of each of the four transmembrane domains (I-IV) of the protein, and contains [[Base (chemistry)|basic]] residues that only allow entry of the positive sodium ions at appropriate membrane voltages by blocking or opening the channel pore. In Ca_v1.1, mutations have also been found in domains II and IV. These mutations are loss-of-function, such that the channels cannot open normally.{{citation needed|date=September 2020}}

In patients with mutations in SCN4A or CACNA1S, therefore, the channel has a reduced excitability and signals from the central nervous system are unable to depolarise the muscle. As a result, the muscle cannot contract efficiently (paralysis). The condition is hypokalemic (manifests when potassium is low; not "causing hypokalemia") because a low extracellular potassium ion concentration will cause the muscle to repolarise to the [[resting potential]] more quickly, so even if calcium conductance does occur it cannot be sustained. It becomes more difficult to reach the calcium threshold at which the muscle can contract, and even if this is reached then the muscle is more likely to relax. Because of this, the severity would be reduced if potassium ion concentrations are kept high.<ref>{{cite journal |vauthors=Rüdel R, Lehmann-Horn F, Ricker K, Küther G |title=Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters |journal=Muscle Nerve |volume=7 |issue=2 |pages=110–20 |date=February 1984 |pmid=6325904 |doi=10.1002/mus.880070205 |s2cid=25705002 }}</ref><ref>{{cite journal |vauthors=Jurkat-Rott K, Lehmann-Horn F |title=Muscle channelopathies and critical points in functional and genetic studies |journal=J. Clin. Invest. |volume=115 |issue=8 |pages=2000–9 |date=August 2005 |pmid=16075040 |pmc=1180551 |doi=10.1172/JCI25525 }}</ref><ref>{{cite journal|last=Kim|first=SJ|author2=Lee, YJ |author3=Kim, JB |title=Reduced expression and abnormal localization of the KATP channel subunit SUR2A in patients with familial hypokalemic periodic paralysis|journal=Biochemical and Biophysical Research Communications|date=January 2010|volume=391|issue=1|pages=974–8|doi=10.1016/j.bbrc.2009.11.177|pmid=19962959}}</ref>

This condition is inherited in an [[autosomal dominant]] pattern (but with a high proportion of sporadic cases), which means one copy of the altered gene in each cell is sufficient to cause the disorder.{{cn|date=July 2021}}

Diagnosis can be achieved through a specialized form of electromyographic (EMG) testing called the long exercise test. This test measures the amplitude of a nerve response (called the Compound Muscle Action Potential or CMAP) for 40 to 50 minutes following a few minutes of exercise. In affected patients, there is a progressive fall in the amplitude of the potential. Besides the patient history or a report of serum potassium low normal or low during an attack, the long exercise test is the current standard for medical testing. Genetic diagnosis is often unreliable as only a few of the more common gene locations are tested, but even with more extensive testing 20–37% of people with a clinical diagnosis of hypokalemic periodic paralysis have no known mutation in the two known genes.<ref>[https://www.ncbi.nlm.nih.gov/books/NBK1338/ "Sternberg D et al. (2009) Hypokalemic Periodic Paralysis, in GeneReviews "]</ref> Standard [[Electromyography|EMG]] testing cannot diagnose a patient unless they are in a full blown attack at the time of testing. Provoking an attack with exercise and diet then trying oral potassium can be diagnostic, but also dangerous as this form of PP has an alternate form known as [[hyperkalemic periodic paralysis]]. The symptoms are almost the same, but the treatment is different. The old [[glucose]] [[insulin]] challenge is dangerous and risky to the point of being life-threatening and should never be done when other options are so readily available.{{Citation needed|date=June 2010}} Factors known to trigger episodes are: stress, cold environment or hypothermia, carbohydrate load, infection, glucose infusion, metabolic alkalosis, alcohol, strenuous exercise, and steroids.{{cn|date=July 2021}}

People with hypokalemic periodic paralysis are often misdiagnosed as having a [[conversion disorder]] or hysterical paralysis since the weakness is muscle-based and doesn't correspond to nerve or spinal root distributions. The tendency of people with hypokalemic periodic paralysis to get paralyzed when epinephrine is released in "fight or flight" situations further adds to the temptation to misdiagnose the disorder as psychiatric.<ref>[httphttps://www.uni-ulm.de/fileadmin/website_uni_ulm/med.inst.040/Dokumente/owner.html "Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F, Hypokalemic periodic paralysis - an owner's manual"]</ref>

Life span is expected to be normal,<ref>{{Cite journal|last=Finsterer|first=J.|date=2008-03-01|title=Primary periodic paralyses|journal=Acta Neurologica Scandinavica|language=en|volume=117|issue=3|pages=145–158|doi=10.1111/j.1600-0404.2007.00963.x|pmid=18031562|s2cid=22496999|issn=1600-0404|doi-access=free}}</ref> but attacks can drop potassium to levels low enough to cause life-threatening breathing problems or heart [[Heart arrhythmia|arrhythmia]]. Patients often report muscle pain and cognitive problems during attacks. [[Migraines]] occur in up to 50% of all hypokalemic periodic paralysis patients and may include less common symptoms like phantom smells, sensitivity to light and sound or loss of words. Medical literatures states that muscle strength is normal between attacks, but patients often report that their baseline strength is in fact lower than that of healthy individuals.{{citation needed|date=February 2016}}

In 1935 the Scottish physician [[Mary Broadfoot Walker|Dr Mary Walker]] was the first to recognise the association between familial periodical paralysis and [[hypokalaemia]]. She also described the glucose challenge test used in diagnosing hypokalaemic periodic paralysis and the use of [[Intravenous therapy|intravenous]] [[potassium]] in its treatment.<ref>{{cite journal | author=Walker MB | title=Potassium chloride in myasthenia gravis | journal=Lancet | year=1935 | volume=2 | pages=47 | doi=10.1016/S0140-6736(01)09382-5 | issue=5836}}</ref><ref>{{Cite book|url=https://books.google.com/books?id=hfjSVIWViRUC&pg=RA3-PA743&lpg=RA3-PA743&dqq=%22jean+hunter+prize%22#v&pg=onepageRA3-PA743|title=Encyclopedia of the Neurological Sciences|date=2014-04-29|publisher=Academic Press|isbn=9780123851581|language=en}}</ref><ref>{{cite journal |vauthors=Aitken RS, Allot EN, Gastelden LI, Walker MB | title=Observations on a case of familial periodic paralysis | journal=Clin Sci | year=1937 | volume=3 | pages=47–57}}</ref>

* {{cite journal |author=Levitt JO |title=Practical aspects in the management of hypokalemic periodic paralysis |journal=J Transl Med |volume=6 |pages=18 |year=2008 |pmid=18426576 |pmc=2374768 |doi=10.1186/1479-5876-6-18 |doi-access=free }} by Dr Jacob O Levitt, a dermatologist who has hypokalemic periodic paralysis.

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