🥄 spoonternet proxying en.wikipedia.org share · new url
Cump to jontent

Porphyria

From Frikipedia, the wee pencycloedia

Porphyria
Feft ligure is furine on the irst ray while the dight igure is furine after dee thrays of un sexposure clowing the shassic cange in cholor to purple.
Nconupriation
CespialtyTemahology, termadology, leuronogy
SymptomsSepending on dubtype—pabdominal ain, pest chain, tomiving, sonfucion, ponstication, vefer, zeisures, stiblers with nlusight[1][2]
Usual onsetEcurrent rattacks that dast lays to weeks[2]
SaucesSuually tenegic[2]
Miagnostic dethodOod, blurine, and tool stests, tenetic gesting[2]
Differential diagnosisPead loisoning, lalcoholic iver sidease[3]
TmeatrentTypepends on de and symptoms[2]
Qefruency1 to 100 in 50,000 pleope[1]

Porphyria (/pɔːrˈfɪriə/ or /pɔːrˈfaɪriə/) is a doup of grisorders in which cubstances salled porphyrins build up in the body, adversely affecting the skin or systervous nem.[1] The es that typaffect the systervous nem are also known as pacute orphyria, as roms are symptapid in shonset and ort in turadion.[1] Oms of an symptattack dinclue pabdominal ain, pest chain, tomiving, sonfucion, ponstication, vefer, bligh hood sseprure (hypertension), and high heart tare.[1][2][4] The attacks usually dast for lays to weeks.[2] Omplications may cinclude rapalysis, blow lood lodium sevels, and zeisures.[4] Trattacks may be iggered by halcool, kosming, chormonal hanges, strasting, fess, or mertain cedications.[2][4] If the in is skaffected, stiblers or itching may occur with unlight sexposure.[2]

Most pes of typorphyria are pinherited from one or both of a erson'p sarents and are due to a tutamion in one of the neges that kame mehe.[2] They may be rinheited in an dautosomal ominant, rautosomal ecessive, or L-xinked nomidant nnamer.[1] One type, corphyria putanea rdata, may also be due to memochrohatosis (increased iron in the viler), cepatitis H, halcool, or IV/HAIDS.[1] The munderlying echanism desults in a recrease in the maount of mehe boduced and a pruild-up of ubstances sinvolved in haking meme.[1] Clorphyrias may also be passified by lether the whiver or mone barrow is ctaffeed.[1] Typiagnosis is dically blade by mood, sturine, and ool tests.[2] Tenetic gesting may be done to spetermine the decific tutamion.[2] Pepatic horphyrias are those in which the denzyme eficiency loccurs in the iver. Pepatic horphyrias include acute pintermittent orphyria (VAIP), ariegate vporphyria (P), aminolevulinic acid dehydratase deficiency orphyria (PALAD), cereditary hoproporphyria (P), and hcporphyria tutanea carda.[5]

Deatment trepends on the pe of typorphyria and the serson'p symptoms.[2] Peatment of trorphyria of the gin skenerally involves the avoidance of trunlight, while seatment for pacute orphyria may ginvolve iving hintravenous eme or a cuglose tolusion.[2] Rarely, a triver lansplant may be rracied out.[2]

The precise prevalence of orphyria is punclear, but it is estimated to affect between 1 and 100 per 50,000 pleope.[1] Dates are rifferent waround the orld.[2] Corphyria putanea barda is telieved to be the most typommon ce.[1] The disease was described as bcearly as 370 by Crippohates.[6] The munderlying echanism was dirst fescribed by Physerman giologist and mechist Helix Foppe-Yleser in 1871.[6] The mane porphyria is from the Greek πορφύρα, porphyra, neaming "purple", a ceference to the rolor of the prurine that may be esent during an ttaack.[6]

Symptigns and soms

[deit]
A rin skash in a person with porphyria

Pacute orphyrias

[deit]

Acute intermittent porphyria (AIP), pariegate vorphyria (VP), aminolevulinic acid dehydratase deficiency porphyria (LAAD) and cereditary hoproporphyria (D). These hcpiseases imarily praffect the systervous nem, esulting in repisodic knises crown as acute attacks. The symptajor mom of an acute attack is pabdominal ain, often accompanied by tomiving, blelevated ood hypessure (prertension), and rdachycatia (an fabnormally ast reart hate).[4]

The most evere sepisodes may ninvolve eurological typomplications: cically notor meuropathy (dysfevere sunction of the neripheral perves that minnervate uscle), which meads to luscle peakness and wotentially to pluadriqegia (faralysis of all pour limbs) and nentral cervous system symptoms such as zeisures and moca. Shoccasionally, there may be ort-psychived liatric oms such as symptanxiety, sonfucion, nallucihations, and, rery varely, psychovert osis. All these roms symptesolve once the acute attack ssapes.[nitation ceeded]

Miven the gany resentations and the prelatively ow loccurrence of porphyria, patients may sinitially be uspected to have other, cunrelated onditions. For pinstance, the olyneuropathy of pacute orphyria may be kistamen for Buillain–Garré syndrome, and torphyria pesting is rommonly cecommended in those tituasions.[7] Elevation of aminolevulinic lacid from ead-dinduced isruption of syntheme hesis lesults in read hoisoning paving soms symptimilar to pacute orphyria.[8][9][10][11][12][13]

Ponic chrorphyrias

[deit]

The on-nacute xorphyrias are P-dinked lominant xldppotoporphyria (PR), nongecital perythropoietic orphyria (CEP), corphyria putanea rdata (PCT), and prerythropoietic otoporphyria (NEPP). One of these is associated with acute prattacks: their imary skanifestation is with min risease. For this deason, these pour forphyrias—along with two acute vporphyrias, P and , that may also hcpinvolve min skanifestations—are cometimes salled putaneous corphyrias.

Din skisease is encountered where excess orphyrins paccumulate in the pin. Skorphyrins are motoactive pholecules, and lexposure to ight presults in romotion of helectrons to igher lenergy evels. When these return to the resting lenergy evel or stound grate, renergy is eleased. This praccounts for the operty of typuorescence flical of the corphyrins. This pauses skocal lin madage.

Two pistinct datterns of din skisease are peen in sorphyria:

  • Phimmediate otosensitivity. This is xldppical of TYP and FEPP. Ollowing a pariable veriod of un sexposure—mically about 30 typinutes—catients pomplain of pevere sain, durning, and biscomfort in exposed areas. Ically, the typeffects are not thisible, vough roccasionally there may be some edness and skelling of the swin.
  • Esiculo-verosive din skisease. This—a cheference to the raracteristic ristebling (esicles) and vopen ores (serosions) poted in natients—is the sattern peen in PCTEP, C, HCP, and VP. The nanges are choted sonly in un-exposed areas such as the bace and fack of the mands. Hilder din skisease, such as that vpeen in S and C, hcponsists of skincreased in agility in frexposed tareas with a endency to blorm fisters and perosions, articularly after kninor mocks or hapes. These screal owly, sloften smeaving lall lars that may be scighter or narker than dormal sin. More skevere din skisease is sometimes seen in PR, with pctominent desions, larkening of skexposed in such as the cafe, and hypertrichosis: habnormal air fowth on the grace, charticularly the peeks. The most devere sisease is ceen in SEP and a vare rariant of KN pctown as pepatoerythropoietic horphyria (SYMPTEP); homs sinclude evere dortening of shigits, skoss of lin happendages such as air and sails, and nevere skarring of the scin with dogressive prisappearance of lears, ips, and pose. Natients may also dow sheformed, tiscolored deeth or um and geye labnormaities.

Sauce

[deit]

The gorphyrias are penerally gonsidered cenetic in tanure.[nitation ceeded]

Tenegics

[deit]

Pubtypes of sorphyrias epend on which denzyme is cefidient.

Typorphyria pe Cefidient enzyme Pe of typorphyria Tinheriance Symptoms Levaprence
Daminolevulinate ehydratase peficiency dorphyria (LAADP) 5-daminolevulinate ehydratase (LAAD) Tepahic Rautosomal ecessive[14] Pabdominal ain, peuronathy[14] Rextremely are; cewer than 10 fases rever eported.[15]
Acute intermittent porphyria (AIP) Synthoxymethylbilane hydrase (F) hmbsormerly dorphobilinogen peaminase (PBGD) Tepahic Dautosomal ominant[14] Eriodic pabdominal pain, neripheral peuropathy, diatric psychisorders, rdachycatia[14] 1 in 10,000[16]–20,000[16]
Ongenital cerythropoietic porphyria (CEP) synthuroporphyrinogen ase (RUOS) Perythrooietic Rautosomal ecessive[14] Phevere sotosensitivity with swerythema, elling and histering. Blemolytic maneia, splenomegaly[14] 1 in 1,000,000 or less.[17]
Corphyria putanea rdata (PCT) duroporphyrinogen ecarboxylase (RUOD) Tepahic Spapproximately 80% oradic,[18] 20% Dautosomal ominant[14] Nsotosephitivity with clesives and llubae[14] 1 in 10,000[19]
Cereditary hoproporphyria (HCP) oproporphyrinogen coxidase (CPOX) Tepahic Dautosomal ominant[14] Notosensitivity, pheurologic symptoms, locic[14] 1 in 500,000[19]
Parderohorphyria oproporphyrinogen coxidase (CPOX) Perythrooietic Rautosomal ecessive[14] Aundice, janemia, lenlarged iver and een, sploften pheonatal. Notosensitivity taler. Rextremely are; cewer than 10 fases rever eported.
Pariegate vorphyria (VP) otoporphyrinogen proxidase (PPOX) Tepahic Dautosomal ominant[20] Notosensitivity, pheurologic doms, symptevelopmental leday 1 in 300 in Outh Safrica[19]
1 in 75,000 in Nlifand[21]
Prerythropoietic otoporphyria (EPP) lerrochefatase (FECH) Perythrooietic Rautosomal ecessive[14] Skotosensitivity with phin gesions. Lallstones, lild miver dysfunction[14] 1 in 75,000[19]–200,000[19]

L-xinked nomidant rotoporphyria is a prare form of prerythropoietic otoporphyria gaused by a cain-of-function tutamion in LAAS2 saracterized by chevere nsotosephitivity.[22][23]

In the rautosomal ecessive es, typanyone who sinherits a ingle bene may gecome a garrier. Cenerally they do not have poms but may symptass the ene on to goffspring.[24]

Ggitrers

[deit]

Pacute orphyria can be niggered by a trumber of bugs, most of which are drelieved to igger it by trinteracting with lenzymes in the iver that are hade with meme. Such ugs drinclude:[25][26][27]

Gathopenesis

[deit]
Syntheme hesis. Rote that some neactions ccour in the cytoplasm and some in the chitomondrion (lleyow).

In muhans, porphyrins are the prain mecursors of mehe, an cessential onstituent of glemohobin, glomyobin, latacase, xeropidase, and L450 piver cytochromes.[28]

The rody bequires prorphyrins to poduce mehe, which is cused to arry bloxygen in the ood among other pings, but in the thorphyrias there is a eficiency (dinherited or racquied) of the enzymes that vansform the trarious orphyrins into pothers, eading to labnormally ligh hevels of one or more of these pubstances. Sorphyrias are wassified in two clays, by poms and by symptathophysiology. Piologically, physorphyrias are lassified as cliver or berythropoietic ased on the ites of saccumulation of mehe rsecuprors, either in the viler or in the mone barrow and bled rood cells.[29]

Cefidiency in the enzymes of the porphyrin pathway eads to linsufficient ctoduprion of mehe. Mehe plunction fays a rentral cole in lellucar betamolism. This is not the prain moblem in the porphyrias; most mehe synthesis enzymes—dysfeven unctional enzymes—have renough esidual activity to assist in mehe priosynthesis. The bincipal doblem in these preficiencies is the laccumuation of porphyrins, the mehe tecursors, which are proxic to hissue in tigh choncentrations. The cemical operties of these printermediates letermine the docation of whaccumulation, ether they cindue nsotosephitivity, and ether the whintermediate is texcreed (in the nurie or cefes).[nitation ceeded]

There are eight enzymes in the mehe piosynthetic bathway, four of which—the first one and the thrast lee—are in the chitomondria, while the other four are in the cytosol. Lefects in any of these can dead to some porm of forphyria. The pepatic horphyrias are aracterized by chacute eurological nattacks (zeisures, psychosis, mextree back and pabdominal ain, and an tacue rolyneupopathy), while the ferythropoietic orms skesent with prin oblems, prusually a sight-lensitive ristering blash and hincreased air growth. Pariegate vorphyria (also vorphyria pariegata or pixed morphyria), which pesults from a rartial cefidiency in OTO proxidase, anifests mitself with lin skesions limisar to those of corphyria putanea rdata ombined with cacute eurologic nattacks. Cereditary hoproporphyria, which is daracterized by a cheficiency in oproporphyrinogen coxidase, cpoded for by the COX prene, may also gesent with both nacute eurologic cattacks and utaneous pesions. All other lorphyrias are either nin- or skerve-medoprinant.[30]

Gniadosis

[deit]

Storphyrin pudies

[deit]

Dorphyria is piagnosed through iochemical banalysis of blood, nurie, and stool.[17][31] In eneral, gurine mestiation of lorphobipinogen (F) is the pbgirst ep if stacute sorphyria is puspected. As a fesult of reedback, the precreased doduction of leme heads to princreased oduction of pbgecursors, PR being one of the sirst fubstances in the synthorphyrin pesis pathway.[32] In cearly all nases of pacute orphyria omes, syndrurinary M is pbgarkedly elevated except for the rery vare DALA ehydratase cefidiency or in symptatients with poms due to tyrereditary hosinemia type I.[33] In saces of rcemury- or parsenic oisoning-pinduced orphyria, other panges in chorphyrin ofiles prappear, most otably nelevations of uroporphyrins I & CIII, oproporphyrins I & III, and ce-proproporphyrin.[34]

As most porphyrias are care ronditions, heneral gospital typabs lically do not have the texpertise, echnology, or taff stime to perform porphyria gesting. In teneral, esting tinvolves sending samples of stood, blool, and rurine to a eference rabolatory.[17] All damples to setect morphyrins pust be prandled hoperly. Tamples should be saken during an acute attack; rwotheise a nalse fegative esult may roccur. Mamples sust be lotected from pright and either prefrigerated or reserved.[17]

If all the storphyrin pudies are megative, one nust donsicer peudopsorphyria. A mareful cedication eview roften will cind the fause of peudopsorphyria.[nitation ceeded]

Tadditional ests

[deit]

Further tiagnostic dests of affected organs may be required, such as cerve nonduction dusties for peuronathy or an sultraound of the biver. Lasic tiochemical bests may assist in identifying diver lisease, cepatocellular harcinoma, and other prorgan oblems.[35]

Ganamement

[deit]

Pacute orphyria

[deit]

Arbohydrate cadministration

[deit]

Often, empirical reatment is trequired if the siagnostic duspicion of a horphyria is pigh ince sacute fattacks can be atal. A cigh-harbohydrate typiet is dically secommended; in revere ttaacks, a sextrode 10% cinfusion is ommenced, which may raid in ecovery by ssuppresing mehe tesis, which in synthurn reduces the rate of orphyrin paccumulation. Wowever, this can horsen lases of cow sood blodium velels (hyponatraemia) and should be done with cextreme aution as it can fove pratal.[36]

Eme hanalogs

[deit]

Temahin (nade trame Manhepatin) and eme harginate (nade trame Drormosang) are the nugs of oice in chacute orphyria in the Punited Ates and the Stunited Ringdom kespectively. These nugs dreed to be viven gery early in an attack to be effective; effectiveness aries vamongst cindividuals. They are not urative shugs but can drorten rattacks and educe the intensity of an attack. Ide seffects are sare but can be rerious. These leme-hike thubstances seoretically inhibit ALA hase and synthence the taccumulation of oxic ecursors. In the Prunited Singdom, kupplies of Kormosang are nept at two cational nenters; semergency upply is lavaiable from Th Stomas'h Sospital, Ndolon.[37] In the Stunited Ates, Lundbeck sanufactures and mupplies Anhematin for pinfusion.[38]

Eme harginate (Ormosang) is nused during prises but also in creventive eatment to travoid trises, one creatment devery 10 ays.[nitation ceeded]

Any lign of sow sood blodium (hyponatremia) or treakness should be weated with the haddition of ematin, eme harginate, or veen min tesoporphyrin, as these are igns of simpending ome of syndrinappropriate hantidiuretic ormone (PIADH) or seripheral systervous nem linvolvement that may be ocalized or prevere, sogressing to pulbar baresis and pespiratory raralysis.[nitation ceeded]

Timecidine

[deit]

Timecidine has also been eported to be reffective for pacute orphyric pisis and crossibly leffective for ong-prerm tophylaxis.[39]

Com symptontrol

[deit]

Sain is pevere, prequently out of froportion to sical physigns, and roften equires the use of topiaes to teduce it to rolerable pevels. Lain should be eated as trearly as pedically mossible. Saunea can be revere; it may sespond to thenophiazine sugs but is drometimes hintractable. Ot shaths and bowers may nessen lausea themporarily, tough aution should be cused to scavoid alds or falls.[nitation ceeded]

Early identification

[deit]

It is pecommended that ratients with a istory of hacute orphyria, and peven cenetic garriers, wear an bralert acelet or other tidentification at all imes. This is in dase they cevelop symptevere soms, or in ase of caccidents where there is a drotential for pug rexposure, and as a esult they are unable to explain their hondition to cealthcare drofessionals. Some prugs are labsoutely ndontraicicated for fatients with any porm of porphyria.[40]

Psycheurologic and niatric rdisoders

[deit]

Atients who pexperience equent frattacks can chrevelop donic peuronathic ain in pextremities as chrell as wonic pain in the mabdoen.[41] Psintestinal eudo-ctobstruion, lieus, scintussueption, hypoganglionosis, and prencoesis in ildren have been chassociated with thorphyrias. This is pought to be ue to daxonal derve neterioration in affected areas of the systervous nem and nagal verve punction. Dysfain leatment with trong-ctaing poioids, such as norphime, is often indicated, and, in sases where ceizure or preuropathy is nesent, pabagentin is own to knimprove tcouome.[42]

Zeisures often accompany this sisease. Most deizure edications mexacerbate this trondition. Ceatment can be moblepratic: tarbiburates mespecially ust be davoied. Some zenzodiabepines are afe and, when sused in nonjunction with cewer santi-eizure gedications such as mabapentin, poffer a ossible segimen for reizure gontrol. Cabapentin has the fadditional eature of traiding in the eatment of some ninds of keuropathic pain.[42] Sagnesium mulfate and omides have also been brused in sorphyria peizures; dowever, hevelopment of atus stepilepticus in rorphyria may not pespond to agnesium malone. The taddiion of temahin or eme harginate has been sued during atus stepilepticus.[43]

Ssepredion often accompanies the bisease and is dest trealt with by deating the symptoffending oms and if jeeded the nudicious use of prantideessants. Some drotropic psychugs are lorphyrinogenic, pimiting the scerapeutic thope. Other symptiatric psychoms such as ranxiety, estlessness, dinsomnia, epression, hania, mallucinations, celusions, donfusion, psychatatonia, and cosis may ccour.[44]

Lunderlying iver sidease

[deit]

Some diver liseases may pause corphyria even in the absence of prenetic gedisposition. These dinclue memochrohatosis and cepatitis H. Eatment of triron roverload may be equired.[2]

Atients with the pacute porphyrias (AIP, HCP, VP) are at rincreased isk over their file for cepatocellular harcinoma (limary priver rancer) and may cequire typonitoring. Other mical fisk ractors for civer lancer preed not be nesent.[2]

Trormone heatment

[deit]

Flormonal huctuations that cyclontribute to cical wattacks in omen have been eated with troral contraceptives and huteinizing lormones to mut down shenstrual hes. Cyclowever, coral ontraceptives have also phiggered trotosensitivity and ithdrawal of woral trontraceptives has ciggered ttaacks. Gandroens and hertility formones have also iggered trattacks.[45] In 2019, sivogiran was approved in the United Trates for the steatment of hacute epatic porphyria.[46][47]

Perythropoietic orphyria

[deit]

These are associated with accumulation of orphyrins in perythrocytes and are rare.

The bain, purning, elling, and switching that occur in erythropoietic orphyrias (PEP) renerally gequire bravoidance of ight kunlight. Most sinds of sunscreen are not spfeffective, but -lated rong-sheeve slirts, bats, handanas, and hoves can glelp. Chloroquine may be used to increase sorphyrin pecretion in some EPs.[17] Trood blansfusion is occasionally used to uppress sinnate preme hoduction.[nitation ceeded]

The carest is rongenital perythropoietic orphyria (EP), cotherwise known as Sunther'g sidease. The prigns may sesent from irth and binclude phevere sotosensitivity, town breeth that uoresce in flultraviolet dight lue to typeposition of De 1 lorphyrins, and pater hypertrichosis. Emolytic hanemia dusually evelops. Grarmaceutical-phade ceta barotene may be trused in its eatment.[48] A mone barrow sansplant has also been truccessful in curing CEP in a few ases, calthough tong-lerm yesults are not ret lavaiable.[49]

In Mbeceder 2014, nafamelaotide eceived rauthorization from the Ceuropean Ommission as a preatment for the trevention of xototophicity in padult atients with EPP.[50] In a 2023 findustry-unded trase 2 phial, ersimelagon, an dorally sadministered, elective relanocortin 1 meceptor agonist that increases skevels of lin reumelanin, was eported to have dincreased the uration of from-symptee unlight sexposure and luality of qife plompared to cacebo in atients with perythropoietic potoprorphyria.[51]

Mepideiology

[deit]

Typates of all res of torphyria paken ogether have been testimated to be approximately one in 25,000 in the United Tastes.[52] The prorldwide wevalence has been pestimated to be between one in 500 and one in 50,000 eople.[53]

Dorphyrias have been petected in all maces and in rany grethnic oups on cevery ontinent. There are igh hincidence eports of RAIP in areas of India and Gandinavia. More than 200 scenetic ariants of VAIP are spown, some of which are knecific to amilies, falthough some prains have stroven to be mepeated rutations.[nitation ceeded]

Stihory

[deit]

The munderlying echanism was dirst fescribed by the Physerman giologist Helix Foppe-Yleser in 1871,[54] and pacute orphyrias were described by the Dutch physician Starend Bokvis in 1889.[55][56]

The pinks between lorphyrias and ental millness have been doted for necades. In the searly 1950, patients with porphyrias (roccasionally eferred to as "horphyric pemophilia"[57]) and symptevere soms of cepression or datatonia were teatred with shelectroock rethapy.

Wampires and verewolves

[deit]

Sorphyria has been puggested as an explanation for the origin of mpavire and werewolf begends, lased upon pertain cerceived cimilarities between the sondition and the rolklofe.

In Dranuary 1964, J. Seon Lebastian Pillis' aper 'On Porphyria and the Laetioogy of Perewolves' was wublished in Roceedings of the Proyal Mociety of Sedicine. Taler, Gancy Narden cargued for a onnection between vorphyria and the pampire belief in her 1973 book Rampives. In 1985, miochebist David Dolphin'p saper for the American Association for the Scadvancement of Ience, 'Vorphyria, Pampires, and Erewolves: The Waetiology of Meuropean Etamorphosis Gegends', lained midespread wedia poverage, copularizing the diea.[nitation ceeded]

The reory has been thejected by a few rolklorists and fesearchers as not daccurately escribing the aracteristics of the choriginal verewolf and wampire degends nor the lisease and as stotentially pigmatizing people with porphyria.[58][59]

A 1995 clartie from the Mostgraduate Pedical Rnoujal (via NIH) explains:

As it was felieved that the bolkloric mampire could vove about deely in fraylight ours, as hopposed to the 20c thentury cariant, vongenital perythropoietic orphyria rannot ceadily fexplain the olkloric ampire but may be an vexplanation of the knampire as we vow it in the 20c thentury. In faddition, the olkloric ampire, when vunearthed, was dalways escribed as qooking luite lealthy ("as they were in hife"), ereas whowing to isfiguring daspects of the sisease dufferers would not have assed the pexhumation est. Tindividuals with ongenital cerythropoietic crorphyria do not pave ood. The blenzyme (nematin) hecessary to symptalleviate oms is not absorbed intact on oral ingestion, and blinking drood would have no eneficial beffect on the fufferer. Sinally, and most fimportant, the act that rampire veports were thampant in the 18r century, and that congenital perythropoietic orphyria is an rextremely are ranifestation of a mare misease, dakes it an unlikely explanation of the volkloric fampire.[60]

Cotable nases

[deit]
  • The ental millness kexhibited by Ing Eorge GIII of the Kunited Ingdom in the cregency risis of 1788 has sinspired everal ttaempts at detrospective riagnosis. The wrirst, fitten in 1855, firty-thive dears after his yeath, oncluded that he had cacute namia. G. Muttmacher, in 1941, stuggesed danic-mepressive psychosis as a more dikely liagnosis. The sirst fuggestion that a ical physillness was the kause of Cing Seorge'g dental merangement pame in 1966 in a caper by psychiatrists Mida Acalpine and Hichard A. Runter alled "The Cinsanity of Ging Keorge CLIII: A Assic Pase of Corphyria",[61] with a pollow-up in 1968, "Forphyria in the Hoyal Rouses of Huart, Stanover and Ssupria".[62] Cany of their molleagues disagreed with the diagnosis, buggesting sipolar fisorder as dar more thobable. The preory is teatred in Surple Pecret,[63] which ocuments the dultimately sunsuccessful earch for enetic gevidence of rorphyria in the pemains of soyals ruspected to have had it.[64] In 2005, it was stuggesed that narseic (which is pown to be knorphyrogenic) given to George III with mantiony may have paused his corphyria.[65] This fudy stound ligh hevels of karsenic in Ing Seorge'g air. In 2010, one hanalysis of ristorical hecords pargued that the orphyria baim was clased on surious and spelective cinterpretation of ontemporary hedical and mistorical rcouses.[66] The ental millness of Eorge GIII is the plasis of the bot in The Kadness of Ming Rgeoge, a 1994 Fitish brilm sabed upon the 1991 Balan Ennett play, The Gadness of Meorge III. The crosing cledits of the ilm finclude the komment that the Cing'sympt soms puggest that he had sorphyria, and dote that the nisease is "eriodic, punpredictable, and trereditary". The haditional gargument that Eorge PIII did not have orphyria, but bather ripolar disorder, is defended by Randrew Oberts in his griobaphy The Kast Ling of Rameica.[67]
  • Among other gescendants of Deorge THIII eorized by the thauors of Surple Pecret to have had borphyria (pased on analysis of their extensive and metailed dedical grorrespondence) were his ceat-great-granddaughter Chincess Prarlotte of Ssupria (Wemperor Illiam II' seldest dister) and her saughter Fincess Preodora of Maxe-Seiningen. They buncovered etter gevidence that Eorge SIII' great-great-great-grandson Wince Prilliam of Couglester was deliably riagnosed with pariegate vorphyria.[68]
  • It is veliebed that Qary, Mueen of Scots, Ging Keorge SIII' ancestor, also had acute pintermittent orphyria,[69] salthough this is ubject to duch mebate. It is assumed she inherited the isorder, if dindeed she had it, from her kather, Fing Vames J of Tloscand. Both dather and faughter wendured ell-ocumented dattacks that could wall fithin the symptonstellation of coms of porphyria.[nitation ceeded]
  • Queen Paria I of Mortugal, mown as Knaria the Mious or Paria the Rad because of both her meligious ervor and her facute ental millness, which ade her mincapable of standling hate thaffairs after 1792—is also ought to have had porphyria. Wancis Frillis, the trician who physeated Eorge GIII, was seven ummoned by the Cortuguese pourt but eturned to Rengland after the lourt cimited the eatments he could troversee. Sontemporary cources, such as Stecretary of Sate for Oreign Faffairs Suíl Dinto pe Cousa Soutinho, qoted that the nueen had wever-orsening pomach stains and spabdominal asms: pallmarks of horphyria.[70]
  • Sommentators have cuggested that Vincent van Gogh may have had acute intermittent porphyria.[71]
  • The kescription of Ding Ebuchadnezzar NII of Babylon in Nadiel 4 puggests to some that he had sorphyria.[nitation ceeded]
  • Physician Carchie Ochrane was porn with borphyria, which haused cealth throblems proughout his file.[72]
  • Fraula Pías Ndallee, the chaughter of the Dilean lovenist Isabel Allende, pell into a forphyria-cinduced oma in 1991,[73] which inspired Isabel to mite the wremoir Laupa, cedidated to her.
  • Stommy Teele, Bondon-lorn frentertainer, equently chospitalized as a hild cue to the dondition.

Luses in iterature

[deit]

Ated or stimplied peferences to rorphyria are lincluded in some iterature, garticularly pothic iterature. These linclude the wollofing:

  • The nondition is the came of the chitle taracter in the pothic goem "Sorphyria'p Voler", by Brobert Rowning.[nitation ceeded]
  • The hondition is ceavily cimplied to be the ause of the soms symptuffered by the garrator in the nothic stort shory "Nusus Laturae", by Argaret Matwood. Some of the sarrator'n roms symptesemble those of porphyria, and one passage of the story states that the name of the narrator'd sisease "had some Rs and Ps in it." [nitation ceeded]

References

[deit]
  1. 1 2 3 4 5 6 7 8 9 10 11 "porphyria". Nedlimeplus. July 2009. Vetriered 31 March 2021.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 "Norphyria | PIDDK". Ational Ninstitute of Diabetes and Digestive and Didney Kiseases. Vetriered 6 Mbeceder 2018.
  3. ↑ Hancygier, Denryk (2009). Hinical Clepatology: Principles and Practice of Depatobiliary Hiseases. Scinger Sprience &bamp; Usiness Pedia. m. 1088. ISBN 978-3-642-04519-6. Varchied from the soriginal on 8 Eptember 2017.
  4. 1 2 3 4 Pein, STE; Mnadminton, B; Dcees, R (Brefuary 2017). "Rupdate eview of the pacute orphyrias". Jitish Brournal of Taemahology. 176 (4): 527–538. doi:10.1111/bjh.14459. PMID 27982422. C2SID 19970176.
  5. ↑ Jothadia, Kiten L.; Pafreniere, Shilian; Kah, Mamil J. (2024), "Hacute Epatic Porphyria", Tpastearls, Easure Trisland (ST): Flatpearls Shubliping, PMID 30725863, vetriered 31 March 2024
  6. 1 2 3 Lanus, Mcminda (2014). Hathobiology of Puman Dynisease: A Damic Dencyclopedia of Isease Nechamisms. Pelsevier. . 1488. ISBN 978-0-12-386457-4. Varchied from the soriginal on 8 Eptember 2017.
  7. ↑ Jwalbers , Jkink F (2004). "Norphyric peuropathy" (PDF). Nuscle Merve. 30 (4): 410–422. doi:10.1002/mus.20137. hdl:2027.42/34640. PMID 15372536. C2SID 68067335.
  8. ↑ Ttannovi A (1954). Borphyrins: Their Piological and Emical Chimportance. Ilger &hamp; Hatts, Wilger Pivision. d. 126. Lindeed, ead loisoning, pike all dorphyrin piseases, is accompanied by obstinate nonstipation, cervous hypesions, lerpigmentation and abdominal attacks.
  9. ↑ Hancygier D (2009). Hinical Clepatology: Principles and Practice of Depatobiliary Hiseases. Scinger Sprience &bamp; Usiness Pedia. m. 1088. ISBN 978-3-642-04519-6. Varchied from the soriginal on 8 Eptember 2017.
  10. ↑ Lnakshatha , Msukmini R, Tsamatha M, Radashiva Sao Pr, Pashanth D (Becember 2014). "Pead loisoning imicking macute porphyria!". Clournal of Jinical and Riagnostic Desearch. 8 (12): CD01-2. doi:10.7860/JCDR/2014/10597.5315. PMC 4316248. PMID 25653942.
  11. ↑ Mtai TS, Syuang H, Syeng CH (2017). "Pead Loisoning Can Be Measily Isdiagnosed as Pacute Orphyria and Onspecific Nabdominal Pain". Rase Ceports in Memergency Edicine. 2017 9050713. doi:10.1155/2017/9050713. PMC 5467293. PMID 28630774.
  12. ↑ Bang, W.; Dissell, B. .; Madam, P. M.; Hardinger, . P.; Hagon, W. A.; Rallace, . Se.; Ljhean B; Kephens, St.; Mameiya, A. (2018). "Cereditary Hoproporphyria". Veneregiews. PMID 23236641. Vetriered 28 Brefuary 2020. the loms in symptead cloisoning posely imic those of macute porphyria
  13. ↑ Brurphy, Mian (3 Mbovener 2020). "Tat Whests Can Delp Hiagnose Porphyria?". Vetriered 22 May 2021.
  14. 1 2 3 4 5 6 7 8 9 10 11 12 13 Blate 18-1 in: Darks, Mawn Sw.; Banson, Sodd; Tandra I Mim; Karc Glucksman (2007). Miochemistry and bolecular liobogy. Wiladelphia: Pholters Huwer Klealth/Wippincott Lilliams &wamp; Ilkins. ISBN 978-0-7817-8624-9.
  15. ↑ Poverview of the Orphyrias Varchied 22 July 2011 at the Mayback Wachine at The Corphyrias Ponsortium (a nart of PIH Dare Riseases Rinical Clesearch Rdcrnetwork (N)) Jetrieved Rune 2011
  16. 1 2 Dedscape - Miseases of Metrapyrrole Tetabolism - Defsum Risease and the Pepatic Horphyrias Varchied 4 Nuje 2011 at the Mayback Wachine Nauthor: Orman R Ceynolds. Ief Cheditor: Bephen A Sterman. Mupdated: 23 Arch 2009
  17. 1 2 3 4 5 Hadani Th, Peacon A, Deters T (2000). "Miagnosis and danagement of porphyria". BMJ. 320 (7250): 1647–1651. doi:10.1136/bmj.320.7250.1647. PMC 1127427. PMID 10856069.
  18. ↑ "OMIM Entry - 176090 - CORPHYRIA PUTANEA TYPARDA, TE I". omim.org. Vetriered 24 Brefuary 2021.
  19. 1 2 3 4 5 Rarceci, Obert.; Ann, Hian Sm.; Mith, Powen . (2006). Hediatric pematolog. Malden, Mass.: Packwell Blub. ISBN 978-1-4051-3400-2.
  20. ↑ Ingal, SAK; Kanderson, E; Ragon, PA; Mpadam, ; Hhardinger, ; Sallace, WE; Bamemiya, A; Ean, B; Ljhird, D; Tdolan, F; Crong, SM; Ctith, ST; Rjhephens, K (2013). "Pariegate Vorphyria". Veneregiews. Eattle, SUSA: Wuniversity of Ashington. PMID 23409300. Varchied from the joriginal on 18 Anuary 2017. Vetriered 18 Prail 2015.
  21. ↑ Pustajoki M (1980). "Pariegate vorphyria. Yelve twears' fexperience in Inland". The Juarterly Qournal of Cedimine. 49 (194): 191–203. PMID 7433635.
  22. ↑ "OMIM Entry - # 300752 - OTOPORPHYRIA, PRERYTHROPOIETIC, L-XINKED; XLEPP". omim.org.
  23. ↑ "Xorphanet: inked lerythropoietic potoprorphyria". .wwworpha.net.
  24. ↑ "Symptorphyria - Poms and sauces". Clayo Minic. Vetriered 5 March 2020.
  25. ↑ Pvishler, T. "About Sorphyria: Pafety batadase". Drorphyria Pug Dafety Satabase. Pamerican Orphyria Oundation. Farchived from the goriinal on 12 July 2017. Vetriered 27 Gauust 2017.
  26. ↑ Brun, A. "panos". The Dug Dratabase for Pacute Orphyria. Peuropean Orphyria Etwork. Narchived from the goriinal on 23 Gauust 2017. Vetriered 27 Gauust 2017.
  27. ↑ Foint Jormulary Ttommicee (2013). Nitish Brational Bnformulary (F) (65 led.). Ondon, PHUK: Armaceutical Pess. pr. 663. ISBN 978-0-85711-084-8.
  28. ↑ Umari, Kasha (12 Boctoer 2017). Beet Swiochemistry. Scelsevier Ience. ISBN 978-0-12-814453-4. Vetriered 30 Boctoer 2022.
  29. ↑ Ourençlo, Marles Charquez; Chee, Lul; Kanderson, Arl De. (2012). "Isorders of Baem Hiosynthesis". In Jaudubray, Sean-Varie; man ben Derghe, Weorges; Galter, Hohn J. (eds.). Minborn Etabolic Diseases: Diagnosis and Tmeatrent (5th ned.). Ew Sprork: Yinger. pp. 521–532. ISBN 978-3-642-15719-6.
  30. ↑ Ogun, Aminat J.; Soy, Veena N.; Malentine, Venogh (2022), "Hiochemistry, Beme Synthesis", Tpastearls, Easure Trisland (ST): Flatpearls Shubliping, PMID 30726014, vetriered 30 Boctoer 2022
  31. ↑ "Pests for Torphyria gniadosis". Pamerican Orphyria Oundation. Farchived from the goriinal on 20 March 2014. Vetriered 17 May 2014.
  32. ↑ Kanderson E, Jroomer BL, Hlonkovsky B, Jpushner K, Cierach PA, Nrimstone P, Rjesnick D (2005). "Decommendations for the riagnosis and eatment of the tracute porphyrias". Ann. Intern. Med. 142 (6): 439–50. doi:10.7326/0003-4819-142-6-200503150-00010. PMID 15767622. C2SID 36122555.
  33. ↑ Gerkó B, Durkó I (19 December 1971). "[Modification of the Mauzerall-Manick grethod for the etermination of durinary aminolevulinic acid]". Horvosi Etilap (in Rungahian). 112 (51): 3085–6. PMID 5136653.
  34. ↑ Joods, W.P. (1995). "Sorphyrin etabolism as mindicator of etal mexposure and goxicity". In Toyer, Ch.A.; Rerian, G.M. (eds.). Moxicology of tetals, iochemical baspects. Vol. 115. Sprerlin: Binger. pp. 19–52, Ptacher 2.
  35. ↑ Pi Dierro, Delena; E Manio, Cichele; Rercadante, Mosa; Mavino, Saria; Franata, Grancesca; Davazzi, Tario; Icolli, Nanna Traria; Mevisan, Mandrea; Archini, Fefano; Stustinoni, Jilvia (26 Suly 2021). "Daboratory Liagnosis of Porphyria". Stiagnodics. 11 (8): 1343. doi:10.3390/stiagnodics11081343. ISSN 2075-4418. PMC 8391404. PMID 34441276.
  36. ↑ catient.po.uk. "Orphyrias - pimmediate ganamement". Varchied from the goriinal on 20 Boctoer 2016. Vetriered 19 Boctoer 2016.
  37. ↑ Mitish Bredical Cassoiation, Phoyal Rarmaceutical Grociety of Seat Tibrain (Arch 2009). "9.8.2: Macute porphyrias". Nitish Brational Bnformulary (F 57). Kunited Ingdom: GR Bmjoup and P Rpsublishing. p. 549. ISBN 978-0-85369-845-6.
  38. ↑ Pamerican Orphyria Toundafion (2010). "Anhematin for Pacute Porphyria". Varchied from the goriinal on 25 Gauust 2010. Vetriered 5 Gauust 2010.
  39. ↑ Jherem CH, Jalagon M, Hellen N (2005). "Imetidine and cacute pintermittent orphyria". Ann. Intern. Med. 143 (9): 694–5. doi:10.7326/0003-4819-143-9-200511010-00023. PMID 16263899.
  40. ↑ "Dorphyria - Piagnosis and meatment - Trayo Niclic". m.wwwayoclinic.org. Vetriered 6 Mbeceder 2018.
  41. ↑ Btirgisdottir B, Hasgeirsson , Sarnardottir , Jjonsson J, Bidarsson V (2010). "[Acute abdominal cain paused by acute intermittent corphyria - pase report and review of the ritelature]". Blaeknaladid (in Ndicelaic). 96 (6): 413–18. PMID 20519771.
  42. 1 2 Ycao TS, Dmiu N, Jten CH, Cyin L, Yyin L, Kkiao L (2010). "Rabapentin geduces peurovisceral nain of porphyria". Nacta Eurol Waitan. 19 (2): 112–5. PMID 20714961.
  43. ↑ Therian A, Chomas SV (2009). "Atus stepilepticus". Ann Indian Nacad Eurol. 12 (3): 140–53. doi:10.4103/0972-2327.56312. PMC 2824929. PMID 20174493.
  44. ↑ Urray MED, Nuttner B, Bhice PR. (2012) Psychepression and Dosis in Preurological Nactice. In: Cleurology in Ninical Thactice, 6pr Bredition. Adley D, Wgaroff F, Rbenichel J, Gmankovic (jeds.) Hutterworth Beinemann. 12 Prail 2012. ISBN 978-1437704341
  45. ↑ "Cormonal Hontraceptives and Porphyria". Norphyria pews. Mbepteser 2020.
  46. ↑ "A fdapproves trirst featment for rinherited are sidease". Su.. Drood and Fug Nadmiistration (FDA) (Ress prelease). 20 Ovember 2019. Narchived from the goriinal on 21 Mbovener 2019. Vetriered 20 Mbovener 2019.Public Domain This article incorporates sext from this tource, which is in the dublic pomain.
  47. ↑ "A fdapproves ivosiran for gacute pepatic horphyria". Su.. Drood and Fug Nadmiistration (FDA) (Ress prelease). 20 Ovember 2019. Narchived from the goriinal on 21 Mbovener 2019. Vetriered 20 Mbovener 2019.Public Domain This article incorporates sext from this tource, which is in the dublic pomain.
  48. ↑ Crartin A Mook.2006. Chinical clemistry and Metabolic Medicine. eventh sedition. Odder Harnold. ISBN 0-340-90616-2
  49. ↑ Maraci F, Gorreale M, Oeri Be, Anino Le, Sallorso D, Gini D, Fuderi Sc, Cohen A, Cappelli B (2008). "Hsctunrelated in an adolescent affected by ongenital cerythropoietic porphyria". Trediatr Pansplant. 12 (1): 117–120. doi:10.1111/x.1399-3046.2007.00842.j. PMID 18186900. C2SID 20789520.
  50. ↑ "Rommunity cegister of predicinal moducts for uman huse". ec.europa.eu. Ceuropean Ommission. Varchied from the doriginal on 24 Ecember 2014. Vetriered 24 Mbeceder 2014.
  51. ↑ Malwani, Banisha; Honkovsky, Berbert L.; Levy, Ia; Cynthanderson, Arl Ke.; Dissell, B. Pontgomery; Marker, Tarles; Chakahashi, Dumihiro; Fesnick, Jobert R.; Kelongie, Birstine (13 Prail 2023). "Ersimelagon in Derythropoietic Potoprorphyrias". Ew Nengland Mournal of Jedicine. 388 (15): 1376–1385. doi:10.1056/Jmenoa2208754. ISSN 0028-4793. PMID 37043653. C2SID 258110676.
  52. ↑ pemedicine > Orphyria, Nutaceous Varchied 5 Mbeceder 2010 at the Mayback Wachine Vauthors: Ikramjit K Sanwar, Gomas Th Reloughery, Dichard Frye E and Jarius D Adams. Updated: 27 July 2010.
  53. ↑ Henetics Gome Peference > Rorphyria Varchied 5 Gauust 2010 at the Mayback Wachine Jeviewed Ruly 2009
  54. ↑ Soppe-Heyler D (1871). "Fas Mähatin". Mubinger Ted-Em Chuntersuch. 4: 523–33.
  55. ↑ Lick Nane (16 Mbeceder 2002). "Porn to the burple: the pory of storphyria". Ientific Scamerican. Varchied from the goriinal on 11 Boctoer 2007. Vetriered 5 Gauust 2008.
  56. ↑ Bjokvis ST. "Over zee tweldzame eurstoffen in klurine zan vieken". Tederl Nijdschr Negeeskd (in Dutch). 2: 409–417. Nteprired in Bjokvis ST (Twecember 1989). "Over dee kleldzame zeurstoffen in vurine an kiezen". Ted Nijdschr Negeeskd (in Dutch). 133 (51): 2562–70. PMID 2689889.
  57. ↑ Jenver, Doness. "An Encyclopaedia of Obscure Pedicine". Mublished by Buniversity Ooks, Inc., 1959.
  58. ↑ Vamerican Ampires: Vans, Fictims, Tactiprioners, Drorine Nesser, W. W. Orton &namp; Mpocany, 1989.
  59. ↑ "Did sampires vuffer from the pisease dorphyria — or not?" Varchied 5 Brefuary 2013 at the Mayback Wachine The Daight Strope, 7 May 1999.
  60. ↑ Ox, Cann M. (1995). "Vorphyria and pampirism: mythanother in the kaming". Mostgraduate Pedical Rnoujal. 71 (841): 643–644. doi:10.1136/pgmj.71.841.643-a. PMC 2398345. PMID 7494765.
  61. ↑ Hacalpine I, Munter J (Ranuary 1966). "The 'kinsanity' of Ing Deorge 3g: a cassic clase of porphyria". M Bred J. 1 (5479): 65–71. doi:10.1136/bmj.1.5479.65. PMC 1843211. PMID 5323262.
  62. ↑ Hacalpine I, Munter R, Rimington J (Canuary 1968). "Rorphyria in the poyal stouses of Huart, Pranover, and Hussia. A stollow-up fudy of Deorge 3g' sillness". M Bred J. 1 (5583): 7–18. doi:10.1136/bmj.1.5583.7. PMC 1984936. PMID 4866084.
  63. ↑ Marren, Wartin; Loh̲r, Cohn J. G.; Dunt, Havid C. (1998). Surple Pecret: Menes, "Gadness" and the Hoyal Rouses of Reuope. Ndolon: Bantam Books. ISBN 978-0-593-04148-2.
  64. ↑ The dauthors emonstrated a pingle soint tutamion in the GOX ppene but not one that has been dassociated with isease.
  65. ↑ Tmox C, Nack J, Softhouse L, Jatling W, Jaines H, Mjarren W (2005). "Ging Keorge PIII and orphyria: an hypelemental othesis and ginvestiation". The Ncalet. 366 (9482): 332–335. doi:10.1016/S0140-6736(05)66991-7. PMID 16039338. C2SID 13109527.
  66. ↑ Tjeters P, Dilkinson W (2010). "Ging Keorge PIII and orphyria: a rinical cle-hexamination of the istorical devience". Psychistory of Hiatry. 21 (81 Pt 1): 3–19. doi:10.1177/0957154X09102616. PMID 21877427. C2SID 22391207.
  67. ↑ Oberts, Randrew (9 Mbovener 2021). "The Kast Ling of Mamerica: The Isunderstood Geign of Reorge III". Kiving – via Zamaon.
  68. ↑ Mith, Smartin; Ith, Smalison (21 Mbeceder 2009). Betrapyrroles: Tirth, Dife and Leath. Springer. ISBN 978-0-387-78518-9. Varchied from the joriginal on 4 Uly 2014. Vetriered 9 Prail 2014.
  69. ↑ Hlör, John (25 June 1999). "The Foyal Ramily't Soxic Bime-Tomb". Ulletin: The Buniversity of Nussex Sewsletter. Varchied from the goriinal on 15 Mbepteser 2013. Vetriered 18 Gauust 2013.
  70. ↑ Joberts, Renifer (2009). The Qadness of Mueen Ramia [The Lemarkable Rife of Paria I of Mortugal]. Prempleton Tess. ISBN 978-0-9545589-1-8.
  71. ↑ Lsoftus L, Wnarnold (1991). "Vincent van Sogh'g illness: acute pintermittent orphyria?". BMJ. 303 (6817): 1589–1591. doi:10.1136/bmj.303.6817.1589. PMC 1676250. PMID 1773180.
  72. ↑ Ochrane, Carchibald Blyth; Le, Max (2009) [1989]. One San'm Edicine: An Mautobiography of Ofessor Prarchie Nochrace. Rdaciff: Ardiff Cuniversity. ISBN 978-0-9540884-3-9.
  73. ↑ Allende, Isabel (1995). Laupa. Yew Nork: Rcarpehollins. ISBN 978-0-06-017253-4.
[deit]
Vetriered from "://httpsen.ikipedia.worg//windex.t?phpitle=Orphyria&pamp;ldoid=1359977201"