{"id":10466,"date":"2008-01-14T14:05:24","date_gmt":"2008-01-14T11:05:24","guid":{"rendered":"https:\/\/www.synevo.ro\/afectiuni\/profil-boala-wilson\/"},"modified":"2020-07-10T12:11:34","modified_gmt":"2020-07-10T09:11:34","slug":"profil-boala-wilson","status":"publish","type":"synevo_diseases","link":"https:\/\/old.synevo.md\/ru\/afectiuni\/profil-boala-wilson\/","title":{"rendered":"Profil boala Wilson"},"content":{"rendered":"<p><strong>Boala Wilson<\/strong> este o afec\u0163iune autozomal-recesiv\u0103, cauzat\u0103 de o muta\u0163ie\/dele\u0163ie la nivelul genei ATP7b de pe bra\u0163ul lung al cromozomului 13, ce codific\u0103 o protein\u0103 transportoare transmembranar\u0103, o ATP-az\u0103, care realizeaz\u0103 at\u00e2t transferul cuprului \u00een <a href=\"\/shop\/ceruloplasmina\/\" class=\"rank-math-link\">ceruloplasmin\u0103<\/a>, c\u00e2t \u015fi excre\u0163ia biliar\u0103 a acestuia. Aceste muta\u0163ii au drept consecin\u0163\u0103 pierderea func\u0163iei de transport a proteinei, urmat\u0103 de:<\/p><ul class=\"wp-block-list\"><li>lipsa \u00eencorpor\u0103rii cuprului \u00een ceruloplasmin\u0103, ce are drept consecin\u0163\u0103 secre\u0163ia unei apoproteine, ce este rapid degradat\u0103, ceea ce explic\u0103 sc\u0103derea nivelului ceruloplasminei \u00een serul pacien\u0163ilor cu boala Wilson;<\/li><li>sc\u0103derea marcat\u0103 a excre\u0163iei biliare a cuprului cu acumularea excesiv\u0103 \u00een hepatocit, ulterior \u015fi \u00een alte \u0163esuturi; efectul toxic celular al cuprului se realizeaz\u0103 prin acumularea de radicali liberi, oxidarea lipidelor, enzimelor \u015fi proteinelor citoscheletale \u015fi inducerea apoptozei celulare, cu apari\u0163ia leziunilor tisulare.<\/li><\/ul><p>Aceste consecin\u0163e reflect\u0103 perturbarea metabolismului cuprului, care caracterizeaz\u0103 boala Wilson. Studiile moleculare ale genei ATP7b la subiec\u0163ii afecta\u0163i au demonstrat existen\u0163a a peste 200 muta\u0163ii distincte, f\u0103r\u0103 a se putea face o corela\u0163ie \u00eentre o anumit\u0103 muta\u0163ie specific\u0103 \u015fi caracteristicile fenotipice ale pacien\u0163ilor.<\/p><p><strong>Clinic <\/strong>boala Wilson se manifest\u0103 extrem de variabil. Semnele \u015fi simptomele sunt rareori prezente \u00eenaintea v\u00e2rstei de 3 ani, probabil datorit\u0103 capacit\u0103\u0163ii crescute de stocare hepatic\u0103 a cuprului. La copii de 10-13 ani, afectarea  ficatului este principala tr\u0103s\u0103tur\u0103 clinic\u0103, semnele neurologice ap\u0103r\u00e2nd \u00een medie o decad\u0103 mai t\u00e2rziu.<\/p><p><strong>Aproximativ 45% din pacien\u0163ii afecta\u0163i prezint\u0103 boal\u0103 hepatic\u0103 cronic\u0103<\/strong>, <strong>35% au semne \u015fi simptome neurologice<\/strong> \u015fi <strong>10% tulburari psihiatrice \u015fi comportamentale<\/strong>. La mai pu\u0163in de 10% dintre cazuri prezentarea ini\u0163ial\u0103 poate include anemie hemolitic\u0103, cardiomiopatie, sindrom Fanconi, osteomalacie sau hipotiroidism, consecin\u0163a injuriei mediate prin cupru.<\/p><p>Spectrul<strong> afect\u0103rii hepatice<\/strong> este variabil \u015fi nespecific: hepatomegalie descoperit\u0103 \u00eent\u00e2mpl\u0103tor, steatoz\u0103 hepatic\u0103, cre\u015fterea asimptomatic\u0103 a aminotransfeazelor, hepatita cronic\u0103 clinic manifest\u0103, ciroza hepatic\u0103 sau insuficien\u0163a hepatic\u0103 rapid evolutiv\u0103. Copii sau adul\u0163ii tineri cu aparent\u0103 hepatit\u0103 autoimun\u0103 care nu r\u0103spund la terapia adecvat\u0103 trebuie examina\u0163i cu aten\u0163ie pentru boala Wilson deoarece hipergamaglobulinemia sau autoanticorpii pot fi prezente \u00een ambele afec\u0163iuni. Dac\u0103 boala nu este diagnosticat\u0103 \u00een fazele ini\u0163iale, cei mai mul\u0163i pacien\u0163i vor progresa inevitabil spre ciroz\u0103 hepatic\u0103 \u015fi hipertensiune portal\u0103. \u00cen cazul \u00een care boala se manifest\u0103 prin insuficien\u0163\u0103 hepatic\u0103 fulminant\u0103, adesea asociat\u0103 cu anemie hemolitic\u0103 Coombs negativ\u0103, hemoglobinurie \u015fi insuficien\u0163\u0103 renal\u0103 acut\u0103, transplantul hepatic este singura solu\u0163ie terapeutic\u0103. Hemoliza acut\u0103 se datoreaz\u0103 eliber\u0103rii masive a cuprului \u00een circula\u0163ie din hepatocitele lezate. Prin urmare, \u00een prezen\u0163a hepatitei severe, hemoliza trebuie \u00eentotdeauna s\u0103 ridice suspiciunea de boala Wilson.<sup>1<\/sup><\/p><p><strong>Tulbur\u0103rile neurologice<\/strong> (ex. tulbur\u0103ri de motricitate, frecvent de tip extrapiramidal) \u015fi psihiatrice (ex. paranoia, deliruri, comportamente de tip schizoid) sunt \u00eentotdeauna \u00eenso\u0163ite de inelele Kaiser-Fleischer (depozite aurii de cupru \u00een membrana Descemet a corneei, f\u0103r\u0103 afectarea vederii).<sup>2<\/sup><\/p><p><strong>Diagnostic.<\/strong> Boala Wilson reprezint\u0103 o provocare pentru clinician datorit\u0103 heterogenicita\u0163ii clinice \u015fi a criteriilor de diagnostic imperfecte. Diagnosticul pozitiv se bazeaz\u0103 pe testele de laborator ce indic\u0103 afectarea metabolismului hepatic al cuprului \u00een prezen\u0163a suspiciunii clinice de boal\u0103. Orice pacient t\u00e2n\u0103r ce prezint\u0103 cre\u015fterea inexplicabil\u0103 a transaminazelor, boal\u0103 hepatic\u0103 progresiv\u0103 \u015fi\/sau simptome neuropsihiatrice trebuie evaluat pentru boala Wilson. Sc\u0103derea nivelului seric al ceruloplasminei se \u00eent\u00e2lne\u015fte la 75% dintre pacien\u0163ii cu afectare hepatic\u0103.<\/p><p>Cu toate acestea, niveluri sc\u0103zute pot fi \u00eent\u00e2lnite \u015fi \u00een alte situa\u0163ii clinice (aceruloplasminemie, malnutri\u0163ie sever\u0103, sindrom nefrotic, hepatopatii severe de alte etiologii, purt\u0103tori heterozigo\u0163i), \u00een timp ce \u00een formele severe de hepatit\u0103 Wilsonian\u0103 ceruloplasmina poate fi normal\u0103. Cupremia poate fi normal\u0103 \u00een hepatita fulminant\u0103, prin eliberarea masiv\u0103 din hepatocitele necrotice. Cre\u015fterea izolat\u0103 a <a href=\"\/shop\/cupru-in-urina\/\" class=\"rank-math-link\">cuprului urinar<\/a> nu este diagnostic\u0103, \u00een schimb cupruria poate fi utilizat\u0103 ca metod\u0103 de monitorizare a eficien\u0163ei tratamentului chelator. Identificarea genei de susceptibilitate (ATP7b) nu a rezolvat pe deplin problema diagnosticului \u00een boala Wilson din cauza heterogenicita\u0163ii alelice \u015fi diponibilit\u0103\u0163ii limitate a testelor moleculare.1<\/p><p>Demonstrarea incapacit\u0103\u0163ii de \u00eencorporare a cuprului radioactiv \u00een ceruloplasmin\u0103 este un test esen\u0163ial \u00een stabilirea diagnosticului bolii Wilson<sup>3<\/sup>, dar de asemenea cu accesibilitate limitat\u0103. \u00cen practic\u0103, dozarea cantitativ\u0103 a cuprului pe fragmentul de \u0163esut hepatic prelevat reprezint\u0103 \u201cstandardul de aur\u201d pentru diagnosticul pozitiv al bolii Wilson, chiar \u00een stadii presimptomatice, fiind de peste 250\u00b5g\/g \u0163esut hepatic uscat. Rezultate fals pozitive se pot \u00eent\u00e2lni \u00een afec\u0163iuni cronice hepatice colestatice, dar rareori sunt atinse valorile \u00eent\u00e2lnite \u00een boala Wilson.<sup>1<\/sup><\/p><div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-1 wp-block-columns-is-layout-flex\"><div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\"><p><strong>Testele screening disponibile \u00een laboratoarele Synevo:<\/strong><\/p><\/div>\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\"><div class=\"synevo-shop-products\">\r\n    <div class=\"sysprod\">\r\n        \r\n        <div class=\"sysprod-products\">\r\n                            <div class=\"sysprod-product\">\r\n                    <a class=\"sysprod-product-title\" href=\"https:\/\/old.synevo.md\/ru\/shop\/cupru-in-sange\/\">Cupru in sange<\/a>\r\n                    <div 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href=\"https:\/\/old.synevo.md\/ru\/shop\/cupru-in-urina\/\">Cupru \u00een urin\u0103<\/a>\r\n                    <div class=\"sysprod-product-price\">\r\n                        <span>Pre\u021b:<\/span>\r\n                        <span>630 lei<\/span>\r\n                    <\/div>\r\n                                            <div class=\"sysprod-product-addcart\">\r\n                            <a\r\n                                href=\"?add-to-cart=9215\"\r\n                                data-quantity=\"1\"\r\n                                class=\"addToCart button product_type_simple add_to_cart_button ajax_add_to_cart \"\r\n                                data-product_id=\"9215\"\r\n                                data-product_sku=\"TOX08\"\r\n                                rel=\"nofollow\"\r\n                            ><div><\/div><\/a>\r\n                        <\/div>\r\n                                    <\/div>\r\n                            <div 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unset;\r\n}\r\n<\/style><\/div><\/div><p><\/p>","protected":false},"featured_media":0,"template":"","synevo_diseases_category":[895],"class_list":["post-10466","synevo_diseases","type-synevo_diseases","status-publish","hentry","synevo_diseases_category-gastroenterologie"],"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/synevo_diseases\/10466","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/synevo_diseases"}],"about":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/types\/synevo_diseases"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=10466"}],"wp:term":[{"taxonomy":"synevo_diseases_category","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/synevo_diseases_category?post=10466"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}