Hyperkalemic periodic paralysis 1017881 221845445 2008-06-26T10:26:40Z Cydebot 1215485 Robot - Moving category Quarter Horses to American Quarter Horses per [[WP:CFD|CFD]] at [[Wikipedia:Categories for discussion/Log/2008 June 16]]. {{Infobox_Disease | Name = Hyperkalemic periodic paralysis | Image = | Caption = | DiseasesDB = 6252 | ICD10 = {{ICD10|G|72|3|g|70}} | ICD9 = {{ICD9|359.3}} | ICDO = | OMIM = 170500 | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = D020513 | }} '''Hyperkalemic periodic paralysis''' ('''HYPP'''), also known as '''Impressive Syndrome''', is an [[genetic disease|inherited]] [[autosomal]] [[dominance relationship|dominant]] disorder which affects [[ion channels|sodium channel]]s in [[muscle]] cells and the ability to regulate [[potassium]] levels in the [[blood]]. It is most commonly associated with [[horses]], but also occurs in [[humans]], where it is also called '''Gamstorp episodic adynamy'''. ==Disease in horses== ===Symptoms and presentation=== This inherited disease is characterized by uncontrollable [[muscle twitching]] and substantial [[muscle weakness]] or [[paralysis]] among affected horses. HYPP is a dominant [[genetic]] disorder; therefore [[Zygosity|heterozygotes]] bred to [[genotype|genotypically]] normal horses have a statistic probability of producing clinically affected offspring 50% of the time. ===Inheritance and prevalence=== Horses affected with HYPP can be treated with some possibility of reducing symptoms, but the degree that medical treatment helps varies from horse to horse. Therefore, horses with HYPP should only be ridden by experienced riders, if anyone, because episodes of paralysis can come on very suddenly and a rider has to be extremely alert to recognize an impending episode which may cause the horse to lose control of its body. The disease is linked to the bloodline of the famous [[American Quarter Horse]] stallion [[Impressive (horse)|Impressive]], who has over 55,000 living descendants [[as of 2003]]. Although the disease is primarily limited to the American Quarter Horse breed and closely related breeds such as [[American Paint Horse]]s and [[Appaloosa]]s at this time, cross-breeding has begun to extend it to [[crossbred]]s recognized by other [[breed registry|breed registries]] as well as [[grade horse]]s. The spread of the disease is perpetuated by the favorable placings given to affected horses in [[halter (horse show)|halter]] competition at [[horse show]]s, because a secondary charactistic associated with N/H and H/H horses is heavy, bulky muscling that is favored by [[stock horse]] judges, a trend that began with Impressive and predates the modern understanding of the disease. ===Genetics=== In 1994, researchers at the [[University of Pittsburgh]], with a grant from various horse organizations, isolated the genetic mutation responsible for the problem and developed a [[blood test]] for it. Using this test, horses may be identified as: * H/H, meaning they have the mutation and it is [[homozygous]]. These horses always pass on the disease. * N/H, meaning they have the mutation and it is [[heterozygous]]. These horses are affected to a lesser degree, and pass on the disease 50% of the time. * N/N, meaning they do not have the mutation and cannot pass it on, even if they are descendants of Impressive. ===Regulation=== Recently, horse organizations have begun instituting rules to attempt to eliminate this widespread disease. The [[American Quarter Horse Association]] (AQHA) now mandates testing for the "Impressive" mutation and will no longer register [[Zygosity|homozygous]] (H/H) foals as of [[2007]], with discussion of [[Zygosity|heterozygous]] (N/H) foals pending. The [[Appaloosa Horse Club]] (ApHC) will no longer accept homozygous foals as of [[2008]]. It is believed that both primary [[palomino]] registries will exclude any foal carrying the "Impressive" mutation as of [[2007]]. The main organization affected by HYPP that has not yet taken action is the [[American Paint Horse Association]] (APHA), although many other smaller organizations are also affected. ==Disease in humans== Although much rarer, hyperkalemic periodic paralysis has also been observed in humans. In humans the disorder causes episodes of extreme muscle weakness, usually beginning in the second decade and depending on the type and severity of the HYPP will increase or stabilize until the fourth or fifth decade where attacks usually decline and can altogether stop. Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, certain pollutants (eg: Cigarette smoke) and periods of fasting. Muscle strength improves between attacks, although many affected people may have increasing bouts of muscle weakness as time goes on (abortive attacks). Sometimes with HYPP those affected may experience degrees of muscle stiffness and spasms (myotonia) in the affected muscles. This can be caused by the same things that trigger the paralysis, dependent on the type of mytonia. (See also paramyotonia). Some people with hyperkalemic periodic paralysis have increased levels of potassium in their blood ([[hyperkalemia]]) during attacks. In other cases, attacks are associated with normal blood potassium levels ([[normokalemia]]). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up. The most common underlying cause is one of several possible [[point mutation]]s in the [[gene]] ''[[SCN4A]]''. The ''SCN4A'' gene provides instructions for making a protein that plays an essential role in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions), including sodium, into muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Mutations in the ''SCN4A'' gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate the flow of sodium ions into muscle cells, which reduces the ability of skeletal muscles to contract. Because muscle contraction is needed for movement, a disruption in normal ion transport leads to episodes of muscle weakness or paralysis. This condition is inherited in an [[autosomal dominant]] pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. ==References== *National Library of Medicine. [http://ghr.nlm.nih.gov/condition=hyperkalemicperiodicparalysis?wf=1 Hyperkalemic periodic paralysis] == External links == * [http://www.vgl.ucdavis.edu/service/horse/hypp.html UC Davis VGL: HYPP genetic test information page] * [http://www.vgl.ucdavis.edu/~lvmillon/hypp/hypp_facts.html UC Davis VGL: Current Facts About Hyperkalemic Periodic Paralysis (HYPP) Disease] * [http://www.bringinglighttohypp.org/ Bringing Light to HyPP] * [http://www.addl.purdue.edu/newsletters/1995/hypp.shtml Purdue Animal Disease Diagnostic Laboratory: HYPP - Still With Us] {{PNS diseases of the nervous system}} {{equidae}} [[Category:Channelopathy]] [[Category:Genetic disorders]] [[Category:Horse diseases]] [[Category:American Quarter Horses]]