{"id":8756,"date":"2019-04-15T09:56:28","date_gmt":"2019-04-15T09:56:28","guid":{"rendered":"https:\/\/jurmed.ro\/medici\/?p=8756"},"modified":"2019-04-15T09:56:28","modified_gmt":"2019-04-15T09:56:28","slug":"amiloidoza-ereditara-tip-transtiretina","status":"publish","type":"post","link":"https:\/\/jurmed.ro\/medici\/amiloidoza-ereditara-tip-transtiretina\/","title":{"rendered":"Amiloidoza ereditar\u0103 tip Transtiretin\u0103"},"content":{"rendered":"

Boal\u0103 genetic<\/em>\u0103 <\/em>rar\u0103, cu prevalen\u021b\u0103 crescut\u0103 \u00een jude\u021bul Suceava<\/em><\/p>\n

Amiloidoza ereditar\u0103 tip transtiretin\u0103 (ATTR) este o boal\u0103 sistemic\u0103 determinat\u0103 de depunerea de fibrile de amiloid formate din variante patologice ale transtiretinei (TTR).<\/p>\n

\u00cen mod normal, transtiretina este o protein\u0103 seric\u0103 cu rol de transportor pentru tiroxin\u0103 \u0219i vitamina A, este sintetizat\u0103 predominant \u00een ficat \u0219i se g\u0103se\u0219te \u00een ser sub form\u0103 de tetramer. \u00cen cazul muta\u021biei genei TTR, apare destabilizarea tetramerul, iar monomerii liberi sufer\u0103 modific\u0103ri conforma\u021bionale ce determin\u0103 agregarea sub forma de fibrile de amiloid.<\/p>\n

ATTR este cea mai frecvent\u0103 form\u0103 de amiloidoz\u0103 familial\u0103, cu o prevalen\u021b\u0103 mondial\u0103 estimat\u0103 la 5000-10.000 de persoane.<\/strong> Exist\u0103 zone considerate endemice, din cauza num\u0103rului crescut de pacien\u021bi diagnostica\u021bi (Nordul Portugaliei<\/strong> \u2013 151\/100.000 de locuitori<\/em>, Nordul Suediei<\/strong> \u2013 104\/100.000 de locuitori<\/em> \u0219i Japonia<\/strong> \u2013 0.99\/1.000.000 de locuitori<\/em>).<\/p>\n

Prevalen\u021ba ATTR \u00een Rom\u00e2nia este de 1.2\/1.000.000 de locuitori si se observ\u0103 o prevalen\u021b\u0103 crescut\u0103 \u00een jude\u021bul Suceava: 3\/100.000 de locuitori.<\/u><\/strong><\/p>\n

Comparativ cu \u021b\u0103rile non-endemice din Europa, \u00een Rom\u00e2nia ATTR este aparent mai rar\u0103 (mult subdiagnosticat\u0103). \u00cen Bulgaria, prevalen\u021ba este de 5.68\/1.000.0001<\/sup> de locuitori, \u00eens\u0103 aceasta este \u00een cre\u0219tere continu\u0103 \u0219i important\u0103 \u00een ultimii ani, ca urmare a test\u0103rii active a popula\u021biei aflate la risc.<\/p>\n

Au fost identificate peste 120 de muta\u021bii \u00een gena TTR, \u00eens\u0103 cea mai frecvent\u0103 muta\u021bie este Val30Met. \u00cen zonele endemice, muta\u021bia Val30Met este cea mai \u00eent\u00e2lnit\u0103, \u00een schimb \u00een zonele non-endemice, exist\u0103 o heterogenitate a muta\u021biilor TTR.<\/p>\n

\u00cen Rom\u00e2nia sunt diagnostica\u021bi 26 de pacien\u021bi cu ATTR. <\/u><\/strong>Dintre ace\u0219tia, 20 prezint\u0103 muta\u021bia Glu54Gln (77%), 3 au muta\u021bia Val30Met, 2 au muta\u021bia Glu89Lys<\/strong>, iar 1 pacient prezint\u0103 muta\u021bia Val122Ile<\/strong>. Este important de men\u021bionat c\u0103 muta\u021bia Glu54Gln pare s\u0103 fie \u00eentalnit\u0103 numai la pacien\u021bii din Rom\u00e2nia<\/u><\/strong>, aceasta fiind pentru prima dat\u0103 descris\u0103 \u00een 2012 <\/strong>de c\u0103tre prof. dr. Daniel Coriu<\/strong>, directorul <\/em>Centrului de Hematologie \u0219i Transplant Medular din Institutul Clinic Fundeni,<\/em> la al XIII-lea Simpozion Interna\u021bional de Amiloidoz\u0103 (ISA).<\/strong><\/p>\n

Trebuie precizat c\u0103 to\u021bi pacien\u021bii cu amiloidoz\u0103 tip transtiretin\u0103 cu muta\u021bia Glu54Gln au originea \u00een jude\u021bul Suceava, \u00een zona Todire\u0219ti.<\/strong><\/p>\n

Debutul bolii \u2013 semnele care indic\u0103 prezen\u021ba ATTR<\/strong><\/p>\n

Prof. dr. Daniel Coriu<\/strong> explic\u0103: \u201eBoala debuteaz\u0103 \u00een jurul v\u00e2rstei de 40 ani cu neuropatie senzitivo-motorie simetric\u0103 (amor\u021beli la nivelul extremit\u0103\u021bilor), progresiv\u0103, la care se asociaz\u0103 unul sau mai multe dintre urm\u0103toarele semne-cheie: istoric familial, disfunc\u021bie autonom\u0103 precoce (disfunc\u021bie erectil\u0103, hipotensiune ortostatic\u0103, tulburare de tranzit intestinal \u2013 diaree, constipa\u021bie, gastroparez\u0103), sc\u0103dere ponderal\u0103 neexplicat\u0103, afectare cardiac\u0103 (cardiomiopatie hipertrofic\u0103, aritmii, blocuri cardiace), sindrom de canal carpian bilateral (mai ales dac\u0103 este prezent \u0219i la al\u021bi membri din familie). Evolu\u021bia este de lung\u0103 durat\u0103, cu agravare progresiv\u0103, cu evolu\u021bia neuropatiei c\u0103tre imobilizare la pat, casexie \u0219i \u00een final deces, dup\u0103 10 ani de la debutul simptomelor.\u201d<\/em><\/p>\n

Diagnosticul ATTR \u2013 simtome specifice \u0219i investiga\u021biile clinice necesare<\/strong><\/p>\n

Pentru stabilirea diagnosticului de ATTR, este necesar\u0103 o anamnez\u0103 minu\u021bioas\u0103, cu analiza atent\u0103 a antecedentelor familiale pentru patologie neurologic\u0103 (parestezii, tulburare de mers, imobilizare la pat), moarte subit\u0103, afectare cardiac\u0103 \u0219i alc\u0103tuire\u0103 arborelui genealogic. Evaluarea antecedentelor personale poate s\u0103 deceleze sindrom de canal\u00a0carpian, tulbur\u0103ri de tranzit intestinal investigat pentru diverse alte patologii sau cardiopatie. Simptomele de prezentare sunt \u00een general paresteziile, tulburare de mers sau imobilizarea la pat, \u00een functie de stadiul bolii, edeme gambiere, dispnee de efort, palpita\u021bii \u0219i sincope, ame\u021beal\u0103 la trecerea \u00een ortostatism din cauza hipotensiunii ortostatice, tulburare de tranzit intestinal, tulbur\u0103ri mic\u021bionale, disfunc\u021bie erectil\u0103, usc\u0103ciunea ochilor\/gurii (sindrom siccca).<\/p>\n

Pe baza datelor clinice, se ridic\u0103 suspiciunea de amiloidoz\u0103 \u0219i se fac investiga\u021biile conform protocolului de diagnostic: analize de s\u00e2nge generale (probe renale, hepatice \u2013 transaminaze, bilirubina, GGT, fosfataza alcalin\u0103, albumina seric\u0103), electroforeza proteinelor serice, imunofixarea proteinelor serice, dozarea imunoglobulinelor \u0219i a lan\u021burilor u\u0219oare libere(excluderea amiloidozei primare), evaluare neurologic\u0103 (consult neurologic, Electromiografie), evaluare cardiologic\u0103 (ECG, NT-proBNP, Troponina, Ecocardiografie, Scintigrafie cu 99m<\/sup> Tc, eventual RMN cardiac), consult oftalmologic (cu Test Schirmer), evaluarea hipotensiunii ortostatice, testarea sistemului nervos vegetativ (SudoScan).<\/p>\n

\u201eEsen\u021biale pentru diagnosticul ATTR sunt secven\u021bierea genei TTR (sau analiza PCR-RFLP pentru muta\u021bia Glu54Gln) \u0219i biopsia din gr\u0103sime abdominal\u0103\/glanda salivar\u0103\/mucoasa rectal\u0103 pentru eviden\u021bierea depozitelor de amiloid (Ro\u0219u de Congo pozitiv, birefringent \u00een lumina polarizat\u0103). De men\u021bionat c\u0103 toate aceste investiga\u021bii sunt disponibile \u00een Institutul Clinic Fundeni din Bucure\u0219ti, unde exist\u0103 o echip\u0103 de medici din specialit\u0103\u021bile: hematologie, cardiologie, neurologie, nefrologie, gastroenterologie, hemopatologie, biologie moleculara, imunochimie dedicat\u0103 acestei boli.\u201d, <\/em>a ad\u0103ugat prof. dr. Daniel Coriu.<\/strong><\/p>\n

Protocolul de investiga\u021bii permite stabilirea diagnosticului de ATTR, varianta de muta\u021bie, organele afectate, gradul de afectare \u0219i ini\u021bierea tratamentului specific. Dup\u0103 diagnosticul pacientului, este necesar\u0103 informarea acestuia \u0219i a rudelor sale cu privire la modul de transmitere autozomal dominant, fenotipul muta\u021biei respective, precum \u0219i despre importan\u021ba diagnosticului \u0219i a tratamentului precoce. Rudele pacientului vor fi testate, dac\u0103 acestea doresc: \u00een primul r\u00e2nd se testeaz\u0103 fra\u021bii, mai ales cei cu v\u00e2rste apropiate cu pacientul, ace\u0219tia av\u00e2nd riscul cel mai mare de a dezvolta boala dac\u0103 prezint\u0103 muta\u021bia ATTR.<\/p>\n

Referin\u021be:<\/em><\/strong><\/p>\n

1<\/sup><\/em>Schmidt HH, Waddington-Cruz M, Botteman MF, et al. Estimating the global prevalence of transthyretin familial amyloid polyneuropathy. Muscle and Nerve. 2018; 57:829-837.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Boal\u0103 genetic\u0103 rar\u0103, cu prevalen\u021b\u0103 crescut\u0103 \u00een jude\u021bul Suceava Amiloidoza ereditar\u0103 tip transtiretin\u0103 (ATTR) este o boal\u0103 sistemic\u0103 determinat\u0103 de depunerea de fibrile de amiloid formate din variante patologice ale […]<\/p>\n","protected":false},"author":1,"featured_media":8757,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-8756","post","type-post","status-publish","format-standard","has-post-thumbnail","category-stiri-noutati"],"yoast_head":"\nAmiloidoza ereditar\u0103 tip Transtiretin\u0103 - Jurmed - Medici<\/title>\n<meta name=\"description\" content=\"Amiloidoza tip transtiretin\u0103 este o boal\u0103 sistemic\u0103 determinat\u0103 de depunerea de fibrile de amiloid formate din variante patologice ale transtiretinei.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/jurmed.ro\/medici\/amiloidoza-ereditara-tip-transtiretina\/\" \/>\n<meta property=\"og:locale\" content=\"ro_RO\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Amiloidoza ereditar\u0103 tip Transtiretin\u0103 - 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