{"id":1050,"date":"2017-01-30T21:46:44","date_gmt":"2017-01-30T20:46:44","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/30\/kongenitalne-poruchy-glykozylacie-a-ich-diagnostika-na-slovensku\/"},"modified":"2017-10-03T10:12:36","modified_gmt":"2017-10-03T08:12:36","slug":"congenital-disorders-of-glycosylation-and-their-diagnosis-in-slovakia","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/congenital-disorders-of-glycosylation-and-their-diagnosis-in-slovakia\/","title":{"rendered":"Congenital disorders of glycosylation and their diagnosis in Slovakia"},"content":{"rendered":"<pre><span style=\"color: #ff0000;\"><strong>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0\r\nattachment at the end of the paper.<\/strong><\/span><\/pre>\n<p>&nbsp;<\/p>\n<p><strong>\u00da<\/strong><strong>vod<\/strong><\/p>\n<p>Kongenit\u00e1lne poruchy glykozyl\u00e1cie (CDG) s\u00fa r\u00fdchlo roz\u0161iruj\u00facou sa skupinou zriedkav\u00fdch dedi\u010dn\u00fdch metabolick\u00fdch ochoren\u00ed, zapr\u00ed\u010dinen\u00fdch poruchou v jednej z najd\u00f4le\u017eitej\u0161\u00edch posttransla\u010dn\u00fdch modifik\u00e1ci\u00ed prote\u00ednov \u2013 glykozyl\u00e1cii. V \u013eudskom tele sa viac ne\u017e polovica v\u0161etk\u00fdch prote\u00ednov a v\u00e4\u010d\u0161ina membr\u00e1nov\u00fdch \u00a0a sekre\u010dn\u00fdch prote\u00ednov (1) nach\u00e1dza v glykozylovanej forme. Glyk\u00e1ny sa kovalentne via\u017eu na prote\u00edny: cez at\u00f3m kysl\u00edka na ser\u00ednov\u00e9 alebo threon\u00ednov\u00e9 zvy\u0161ky (O-viazan\u00e9 oligosacharidy) alebo cez at\u00f3m dus\u00edka na asparag\u00ednov\u00e9 zvy\u0161ky prote\u00ednov (N-viazan\u00e9 oligosacharidy) (2).<\/p>\n<p>V posledn\u00fdch rokoch sa postupne \u00a0za\u010dal zis\u0165ova\u0165 vz\u0165ah medzi aberantnou glykozyl\u00e1ciou a mnoh\u00fdmi ochoreniami. Zmeny v glykozyla\u010dnom profile boli zisten\u00e9 u pacientov trpiacich Alzheimerovou chorobou (3) a vo viacer\u00fdch biomarkeroch u pacientov trpiacich r\u00f4znymi typmi n\u00e1dorov\u00fdch ochoren\u00ed bolo potvrden\u00e9, \u017ee onkogen\u00e9za je \u010dasto v korela\u010dnom vz\u0165ahu so zmenami v oligosacharidovej \u0161trukt\u00fare (4). Glykozyla\u010dn\u00fd \u00a0proces je komplexn\u00fd a zah\u0155\u0148a stovky \u0161pecifick\u00fdch \u00a0enz\u00fdmov, transport\u00e9rov. Z\u00fa\u010dast\u0148uje sa ho 250 \u2013 500 g\u00e9nov, \u010do reprezentuje 1 % z cel\u00e9ho \u013eudsk\u00e9ho gen\u00f3mu (5). V roku 1997 boli zn\u00e1me \u00a0tri defekty g\u00e9nov z\u00fa\u010dast\u0148uj\u00facich \u00a0sa N-glykozyla\u010dn\u00e9ho procesu, v roku 2011 bolo v\u010faka neust\u00e1lemu \u00a0rozvoju modern\u00fdch analytick\u00fdch met\u00f3d zn\u00e1mych pribli\u017ene 50 subtypov t\u00fdchto ochoren\u00ed\u00a0 (6). Po\u010det zn\u00e1mych \u00a0subtypov neust\u00e1le narast\u00e1 (7) a predpoklad\u00e1 sa, \u017ee mnoho \u00a0pacientov st\u00e1le zost\u00e1va nediagnostikovan\u00fdch (obr\u00e1zok 1). U pribli\u017ene 40 % CDG pacientov konkr\u00e9tny enzymatick\u00fd defekt, a teda aj molekul\u00e1rna podstata t\u00fdchto ochoren\u00ed zost\u00e1va st\u00e1le neobjasnen\u00e1.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Kli<\/strong><strong>ni<\/strong><strong>c<\/strong><strong>k<\/strong><strong>\u00e9 pr\u00edznaky<\/strong><\/p>\n<p>Porucha v jedinom g\u00e9ne z\u00fa\u010dast\u0148uj\u00facom sa glykozyla\u010dn\u00e9ho procesu vedie k \u0161irokej \u0161k\u00e1le sympt\u00f3mov, ktor\u00e9 potenci\u00e1lne zasiahnu viacer\u00e9 org\u00e1ny a klinick\u00e9 pr\u00edznaky s\u00fa ve\u013emi ne\u0161pecifick\u00e9. CDG m\u00f4\u017ee postihn\u00fa\u0165 ak\u00fdko\u013evek org\u00e1n \u013eudsk\u00e9ho tela, av\u0161ak v\u00e4\u010d\u0161inou tieto ochorenia \u00a0b\u00fdvaj\u00fa multisyst\u00e9- mov\u00e9 a postihuj\u00fa jeden alebo viacer\u00e9 org\u00e1ny. M\u00f4\u017eu by\u0165 \u017eivot ohrozuj\u00face, ale aj s miernym priebehom. CDG patria do skupiny \u0165a\u017eko diagnostikovate\u013en\u00fdch ochoren\u00ed pre ich \u010dastokr\u00e1t ne\u0161pecifick\u00fa klinick\u00fa manifest\u00e1ciu ochorenia. Mnoh\u00e9 CDG s\u00fa charakteristick\u00e9 poruchami \u00a0v centr\u00e1lnom nervovom syst\u00e9me (hypot\u00f3nia, z\u00e1chvaty, oneskoren\u00fd \u00a0v\u00fdvoj, kognit\u00edvne poruchy a cerebel\u00e1rna\u00a0 hypopl\u00e1zia ved\u00faca \u00a0k probl\u00e9mom \u00a0s rovnov\u00e1hou a koordin\u00e1ciou). \u010eal\u0161\u00edmi sympt\u00f3mami s\u00fa hepatopatia, kardiomyopatia, abnorm\u00e1lna distrib\u00facia tuku, koagula\u010dn\u00e9 poruchy, gastrointestin\u00e1lne \u0165a\u017ekosti, strabizmus, tv\u00e1rov\u00fd dysmorfizmus, poruchy preh\u013atania a poruchy rastu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>M<\/strong><strong>o<\/strong><strong>\u017e<\/strong><strong>nos<\/strong><strong>t<\/strong><strong>i diagnostiky<\/strong><\/p>\n<p>V s\u00fa\u010dasnosti je alarmuj\u00faci neust\u00e1le rast\u00faci tlak na skr\u00edning a diagnostiku tejto skupiny dedi\u010dn\u00fdch metabolick\u00fdch por\u00fach v na\u0161ej krajine. Napriek tomu, \u017ee CDG s\u00fa vroden\u00fdmi metabolick\u00fdmi poruchami, nie s\u00fa s\u00fa\u010das\u0165ou novorodeneck\u00e9ho skr\u00edningov\u00e9ho programu. Pacienti s kongenit\u00e1lnymi poruchami N- a O-glykozyl\u00e1cie s\u00fa zachyt\u00e1van\u00ed cestou selekt\u00edvneho skr\u00edningu na z\u00e1klade \u0161pecifick\u00fdch klinick\u00fdch sympt\u00f3mov a laborat\u00f3rnych n\u00e1lezov. S neust\u00e1lym rozvojom robustn\u00fdch analytick\u00fdch met\u00f3d vo svete st\u00fapa aj zn\u00e1ma prevalencia, zatia\u013e \u010do molekul\u00e1rna podstata ost\u00e1va v mnoh\u00fdch pr\u00edpadoch st\u00e1le neobjasnen\u00e1.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Izoelektrick\u00e1 fokus\u00e1cia<\/strong><\/p>\n<p>V roku 2012 bola v Centre dedi\u010dn\u00fdch metabolick\u00fdch por\u00fach (CDMP) DFNsP Bratislava zaveden\u00e1 met\u00f3da selekt\u00edvneho skr\u00edningu CDG zalo\u017een\u00e1 na izoelektrickej fokus\u00e1cii (IEF) s\u00e9rov\u00e9ho transfer\u00ednu. T\u00e1to met\u00f3da v s\u00fa\u010dasnosti predstavuje zlat\u00fd \u0161tandard uplat\u0148uj\u00faci sa v\u0161ade vo svete na z\u00e1chyt pacientov s poruchami glykozyl\u00e1cie. CDMP je v s\u00fa\u010dasnosti jedin\u00e9 pracovisko na Slovensku, ktor\u00e9 sa zaober\u00e1 skr\u00edningom CDG. Tento test rozde\u013euje glykoizoformy na z\u00e1klade n\u00e1boja, \u010d\u00edm umo\u017e\u0148uje odl\u00ed\u0161i\u0165 zdrav\u00fdch jednotlivcov od suspektn\u00fdch pacientov s poruchou \u00a0N-glykozyl\u00e1cie podtypu I alebo \u00a0II. U CDG I pacienta \u00a0je v IEF profile pr\u00edtomn\u00fd \u00a0asialoa vo ve\u013ekom mno\u017estve \u00a0disialotransfer\u00edn, k\u00fdm tetrasialotransfer\u00edn sa v s\u00e9re nach\u00e1dza v ni\u017e\u0161ej koncentr\u00e1cii v porovnan\u00ed s kontrolnou vzorkou s\u00e9ra od zdrav\u00e9ho jedinca (pozri obr\u00e1zok 2) (8). Z\u00edskan\u00fd patologick\u00fd profil glykoizoforiem v\u0161ak nevypoved\u00e1 o konkr\u00e9tnom enzymatickom \u00a0deficite. Okrem prim\u00e1rnych por\u00fach \u00a0N-glykozyl\u00e1cie \u00a0I. a II. podtypu \u00a0zachyt\u00e1va \u00a0CDMP aj sekund\u00e1rne patologick\u00fd \u00a0profil v obraze IEF transfer\u00ednu u pacientov s heredit\u00e1rnou intoleranciou \u00a0frukt\u00f3zy, galaktoz\u00e9miou, z\u00e1vislos\u0165ou od alkoholu, ale aj pri polymorfizme transfer\u00ednu, \u0165a\u017ek\u00fdch ochoreniach \u00a0pe\u010dene a u pacientov s hemolyticko-uremick\u00fdm \u00a0syndr\u00f3mom. IEF s\u00e9rov\u00e9ho \u00a0transfer\u00ednu teda umo\u017e\u0148uje \u00a0detegova\u0165 \u00a0glykozyla\u010dn\u00e9 defekty ved\u00face k zn\u00ed\u017eenej sialyz\u00e1cii, av\u0161ak neposkytuje dostato\u010dn\u00e9 rozl\u00ed\u0161enie potrebn\u00e9 na objasnenie \u0161pecifick\u00fdch enzymatick\u00fdch \u00a0defektov, a teda neumo\u017e\u0148uje \u00a0diagnostiku konkr\u00e9tneho subtypu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>\u0160trukt\u00farna anal\u00fdza N-viazan\u00fdch glyk\u00e1nov<\/strong><\/p>\n<p>Na \u010fal\u0161iu diagnostiku \u0161pecifick\u00e9ho subtypu a konkr\u00e9tneho enzymatick\u00e9ho deficitu vznikla spolupr\u00e1ca medzi \u00a0klinikmi a vedcami z Centra excelentnosti pre glykomiku (CEG), Chemick\u00fd \u00a0\u00fastav SAV, ktor\u00e1 otv\u00e1ra nov\u00e9 mo\u017enosti v personalizovanej medic\u00edne. Vzorky od pacientov s pozit\u00edvnym v\u00fdsledkom skr\u00edningu sa spracuj\u00fa pr\u00edstupom anal\u00fdzy N-glykoprofilu celkov\u00e9ho s\u00e9ra alebo anal\u00fdzy N-glykoprofilu zvolen\u00e9ho biomarkera (napr\u00edklad s\u00e9rov\u00e9ho transfer\u00ednu) izolovan\u00e9ho imunoafinitnou preparat\u00edvnou chromatografiou. N-glyk\u00e1ny s\u00fa uvo\u013enen\u00e9 prostredn\u00edctvom enzymatickej deglykozyl\u00e1cie, frakcionovan\u00e9 a fluorescen\u010dne zna\u010den\u00e9 za \u00fa\u010delom stanovenia ich \u0161trukt\u00far pomocou \u00a0LC-MS (tzv. \u201eoffline\u201c prepojenie HIAX HPLC chromatografie a MALDI TOF\/ TOF hmotnostnej spektrometrie).<\/p>\n<p>Reprezentat\u00edvna anal\u00fdza sialylovanej frakcie celkov\u00e9ho N-glykoprofilu \u013eudsk\u00e9ho s\u00e9ra je zobrazen\u00e1 \u00a0na obr\u00e1zku 3. Pr\u00edpadn\u00e9 zmeny\u00a0 v \u0161pecifickom kroku synt\u00e9zy N-glyk\u00e1nov\u00fdch \u00a0\u0161trukt\u00far s\u00fa tak detegovate\u013en\u00e9 \u00a0na kvanti- tat\u00edvnej \u00a0i kvalitat\u00edvnej \u00a0\u00farovni, v\u010faka \u010domu m\u00f4\u017eu by\u0165 predpokladom pre vybran\u00fd konkr\u00e9tny enzymatick\u00fd \u00a0defekt. T\u00fdm sa mnohon\u00e1sobne zu\u017euje okruh potenci\u00e1lnych \u00a0kandid\u00e1tnych glykog\u00e9nov z\u00fa\u010dast\u0148uj\u00facich \u00a0sa glykozyla\u010dn\u00e9ho procesu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>\u0160trukt\u00farna anal\u00fdza O-viazan\u00fdch glyk\u00e1nov apolipoprote\u00ednu CIII<\/strong><\/p>\n<p>V CEG Chemick\u00e9ho \u00a0\u00fastavu SAV bola na sledovanie pr\u00edpadn\u00fdch por\u00fach v O-glykozyl\u00e1cii v roku 2015 zaveden\u00e1 met\u00f3da stanovenia O-glykoprofilu apolipoprote\u00ednu CIII (9). S\u00e9rov\u00e9 lipoprote\u00ednov\u00e9 \u00a0komplexy \u00a0s\u00fa mechanicky rozbit\u00e9 a n\u00e1sledne je vzorka odsolen\u00e1 pomocou \u00a0chromatografie na reverznej f\u00e1ze. V MALDI TOF hmotnostnom spektre takto pripravenej vzorky je mo\u017en\u00e9 \u00a0pozorova\u0165 \u00a0jednotliv\u00e9 \u00a0sign\u00e1ly prisl\u00fachaj\u00face \u00a0asialo-, monosialo- a disialo-O-glykoizoform\u00e1m, ktor\u00fdch relat\u00edvny pomer a jeho zmeny m\u00f4\u017eu vypoveda\u0165 o poruch\u00e1ch v procesoch O-glykozyl\u00e1cie.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Sekvenovanie novej gener\u00e1cie<\/strong><\/p>\n<p>\u010eal\u0161ie mo\u017enosti otv\u00e1ra anal\u00fdza na \u00farovni DNA, pri ktorej sa na z\u00e1klade \u0161trukt\u00farneho profilu glyk\u00e1nov vymedz\u00ed s\u00fabor potenci\u00e1lne postihnut\u00fdch glykog\u00e9nov. Takto vytipovan\u00e9 \u00a0g\u00e9ny s\u00fa \u010falej podroben\u00e9 genomickej anal\u00fdze na zistenie mut\u00e1ci\u00ed potenci\u00e1lne \u00a0zodpovedn\u00fdch \u00a0za vznik tohto typu ochoren\u00ed. Testovanie na \u00farovni jedn\u00e9ho g\u00e9nu nem\u00e1 v\u00fdznam, preto\u017ee presn\u00e1 pr\u00ed\u010dina vzniku ochorenia \u00a0nie je zn\u00e1ma. V pr\u00edpade symptomatiky CDG ochoren\u00ed ide o multisyst\u00e9mov\u00e9 zlyhanie, a to utv\u00e1ra predpoklad, \u017ee sa sledovan\u00e1 mut\u00e1cia m\u00f4\u017ee vyskytova\u0165 v ktoromko\u013evek z g\u00e9nov (jednom \u010di viacer\u00fdch) z\u00fa\u010dast\u0148uj\u00facich sa biosyntetickej dr\u00e1hy glyk\u00e1nov. Na anal\u00fdzu glykog\u00e9nov bude preto pou\u017eit\u00e9 sekvenovanie novej gener\u00e1cie ako ve\u013emi robustn\u00e1 met\u00f3da, pri ktorej je mo\u017en\u00e9 \u00a0s\u00fa\u010dasne analyzova\u0165 viacer\u00fdch pacientov a ve\u013ek\u00e9 mno\u017estvo g\u00e9nov v jednom sekvena\u010dnom behu. Neust\u00e1le zni\u017eovanie ceny, zjednodu\u0161ovanie \u00a0pr\u00edpravy vzoriek a \u010doraz v\u00e4\u010d\u0161ie mno\u017estvo d\u00e1t z\u00edskan\u00fdch z jedin\u00e9ho sekvena\u010dn\u00e9ho behu rad\u00ed t\u00fato met\u00f3du medzi progres\u00edvne sa rozv\u00edjaj\u00face met\u00f3dy v diagnostike \u00a0aj v z\u00e1kladnom\u00a0v\u00fdskume. Na anal\u00fdzu vytipovan\u00fdch g\u00e9nov sa pou\u017e\u00edvaj\u00fa prednastaven\u00e9 panely g\u00e9nov dod\u00e1van\u00e9 v\u00fdrobcom. Analyzuj\u00fa sa cel\u00e9 ex\u00f3ny vopred vytipovan\u00fdch g\u00e9nov postihnut\u00fdch jedincov, ako aj parent\u00e1lnej gener\u00e1cie na zistenie genetick\u00e9ho pozadia CDG ochoren\u00ed (10).<\/p>\n<p>Sekvenovan\u00edm ex\u00f3nov\u00fdch \u010dast\u00ed kandid\u00e1tnych g\u00e9nov sa nemusia za- chyti\u0165 v\u0161etky mut\u00e1cie sp\u00f4sobuj\u00face ochorenie. Existuje toti\u017e predpoklad, \u017ee pribli\u017ene 15 % pacientov m\u00e1 mut\u00e1ciu v nek\u00f3duj\u00facich \u00a0oblastiach sledovan\u00fdch g\u00e9nov. Z tohto d\u00f4vodu \u00a0je nevyhnutn\u00e9 \u00a0podrobi\u0165 sekven\u010dnej anal\u00fdze nielen oblasti, v ktor\u00fdch doch\u00e1dza \u00a0k zostrihu, ale aj hlbok\u00e9 intr\u00f3nov\u00e9 oblasti sledovan\u00fdch \u00a0g\u00e9nov \u00a0(11).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>P<\/strong><strong>e<\/strong><strong>r<\/strong><strong>sp<\/strong><strong>e<\/strong><strong>k<\/strong><strong>t<\/strong><strong>\u00ed<\/strong><strong>v<\/strong><strong>a CDG<\/strong><\/p>\n<p>Objav vhodn\u00fdch terapeutick\u00fdch pr\u00edstupov v lie\u010dbe CDG st\u00e1le ost\u00e1va v\u00fdznamnou v\u00fdzvou, nako\u013eko sa celkov\u00e1 prevalencia t\u00fdchto ochoren\u00ed v USA odhaduje a\u017e na 1 : 10 000 (7). V priebehu roku 2013 bol vo svete nov\u00fd zn\u00e1my CDG subtyp reportovan\u00fd ka\u017ed\u00fdch 17 dn\u00ed, a to pr\u00e1ve v\u010faka v\u00fdvoju st\u00e1le citlivej\u0161\u00edch analytick\u00fdch met\u00f3d, ktor\u00e9 s\u00fa dnes dostupn\u00e9 aj na p\u00f4de Slovenskej republiky. Napriek obrovsk\u00e9mu rozvoju diagnostick\u00fdch mo\u017enost\u00ed sa v\u0161ak st\u00e1le predpoklad\u00e1, \u017ee v\u00e4\u010d\u0161ina CDG pacientov ost\u00e1va poddiagnostikovan\u00fdch. Od roku 2012 je v na\u0161ej krajine dostupn\u00e1 efekt\u00edvna skr\u00edningov\u00e1 met\u00f3da, ktor\u00e1 umo\u017e\u0148uje z\u00e1chyt pacientov s CDG. Na lep\u0161ie poznanie CDG a pr\u00ed\u010din ich vzniku bude preto v bud\u00facnosti nevyhnutn\u00e1 u\u017e\u0161ia spolupr\u00e1ca\u00a0 medzi v\u00fdskumn\u00fdmi\u00a0 pracoviskami a diagnostick\u00fdmi laborat\u00f3riami. Len aplik\u00e1ciou molekul\u00e1rno-biologick\u00fdch d\u00e1t v spolupr\u00e1ci s poznatkami o glykozyl\u00e1cii prote\u00ednov sa umo\u017en\u00ed roz\u0161irovanie panelu kandid\u00e1tnych g\u00e9nov potenci\u00e1lne zodpovedn\u00fdch za tento typ ochoren\u00ed (5). Na diagnostiku por\u00fach \u00a0s\u00favisiacich s metabolizmom glykokonjug\u00e1tov je preto limituj\u00face zavedenie r\u00fdchlych, presn\u00fdch a spo\u013eahliv\u00fdch met\u00f3d.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Z<\/strong><strong>\u00e1<\/strong><strong>ver<\/strong><\/p>\n<p>Poruchy glykozyl\u00e1cie s\u00fa v na\u0161ej krajine poddiagnostikovan\u00e9 z r\u00f4znych d\u00f4vodov: neuspokojiv\u00e9 \u00a0lek\u00e1rske povedomie, vysok\u00e1 mortalita v prvom roku \u017eivota, ako aj nedostupnos\u0165 v minulosti \u0161tandardn\u00e9ho skr\u00edningo- v\u00e9ho laborat\u00f3rneho testu. Ke\u010f\u017ee ide o zriedkav\u00e9 ochorenia, \u00faspe\u0161nos\u0165 z\u00e1chytu \u00a0i d\u00f4kladn\u00e1 \u00a0diagnostika, a\u017e na \u00farovni \u0161trukt\u00farnej anal\u00fdzy glyk\u00e1nov \u010di muta\u010dnej anal\u00fdzy cel\u00fdch panelov glykog\u00e9nov, z\u00e1vis\u00ed aj od dobrej spolupr\u00e1ce klinick\u00fdch pracov\u00edsk s pracoviskami v\u00fdskumn\u00e9ho, respekt\u00edve akademick\u00e9ho charakteru. Iba v\u010dasn\u00e1 a presn\u00e1 diagnostika dok\u00e1\u017ee napom\u00f4c\u0165 stanoveniu spr\u00e1vnej diagn\u00f3zy u pacienta, pr\u00edpadne prenat\u00e1lnej diagnostiky pri \u010fal\u0161ej gravidite matky, pochopeniu molekul\u00e1rnej podstaty t\u00fdchto ochoren\u00ed, ako aj zabr\u00e1neniu pr\u00edpadn\u00e9ho ireverzibiln\u00e9ho po\u0161kodenia organizmu.<\/p>\n<p><em>P<\/em><em>o<\/em><em>\u010fakovanie: <\/em><em>T<\/em><em>\u00e1<\/em><em>t<\/em><em>o publik\u00e1cia vznikla v\u010faka podpore v r\u00e1mci <\/em><em>op<\/em><em>e<\/em><em>r<\/em><em>a<\/em><em>\u010d<\/em><em>n<\/em><em>\u00e9<\/em><em>ho <\/em><em>programu V\u00fdskum <\/em><em>a v\u00fdvoj pre projekt: Centrum excelentnosti pre glykomiku, ITMS 26240120031, spolufinancovan\u00fd zo zdrojov Eur\u00f3pskeho fondu region\u00e1l- neho rozvoja. Osobitn\u00e9 po\u010fakovanie patr\u00ed aj cel\u00e9mu Centru dedi\u010dn\u00fdch metabolick\u00fdch por\u00fach v Bratislave za vysoko odborn\u00fa spolupr\u00e1cu tohto klinick\u00e9ho pracoviska s Chemick\u00fdm \u00fastavom SAV.<\/em><\/p>\n<p>&nbsp;<\/p>\n<p><strong>L<\/strong><strong>it<\/strong><strong>e<\/strong><strong>ra<\/strong><strong>t<\/strong><strong>\u00fa<\/strong><strong>ra<\/strong><br \/>\n1. Durand G, Seta N. Protein Glycosylation and diseases: Blood and urinary oligosaccharides as markers for diagnosis and therapeutic monitoring. Clin Chem. 2000;46(6):795\u2013805.<br \/>\n2. Sol\u00e1 RJ, Griebenov K. Glycosylation of Therapeutic Proteins: An Effective Strategy to Optimize Efficacy. BioDrugs. 2010;24(1):9\u201321.<br \/>\n3. Abou-Abbass H, Abou-El-Hassan H, Bahmad H, et al. Glycosylation and other PTMs alterations in neurodegenerative diseases: Current status and future role in neurotrauma. Electroph. 2016; published online.<br \/>\n4. Ferreira JA, Magalh\u00e3es A, Gomes J, et al. Protein glycosylation in gastric and colorectal cancers: Toward cancer detection and targeted therapeutics. Canc Letters. 2016; in press.<br \/>\n5. Jones MA, Hegde MR. Congenital Disorders of Glycosylation. Molecular Pathology in Clinical Practice. New York: Springer International Publishing; 2016: 121\u2013125.<br \/>\n6. Morava E, Lefeber D. CDG \u2013 an update. J Inherit Metab Dis. 2011;34(4):847\u201348.<br \/>\n7. Freeze HH. Understanding human glycosylation disorders: Biochemistry leads the charge. J Biol Chem. 2013;288:6936\u201345.<br \/>\n8. D\u00f6rre K, Olczak M, Wada Y, et al. A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach. J Inh Met Dis. 2015;38(5):931\u2013940.<br \/>\n9. Wada Y, et al. Mass spectrometry of apolipoprotein C-III, a simple analytical method for mucin-type O-glycosylation and its application to an autosomal recessive cutis laxa type-2 (ARCL2) patient. Glycobiol. 2012;22(8):1140\u20131144.<br \/>\n10. Jones MA, Rhodenizer D, da Silva C, et al. Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing. Mol gen metab. 2013;110(1):78\u201385.<br \/>\n11. Raffan E, Semple RK. Next generation sequencing-implications for clinical practise. Brit Med Bull. 2011;99:53\u201371.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper. &nbsp; \u00davod Kongenit\u00e1lne poruchy glykozyl\u00e1cie (CDG) s\u00fa r\u00fdchlo roz\u0161iruj\u00facou sa skupinou zriedkav\u00fdch dedi\u010dn\u00fdch metabolick\u00fdch ochoren\u00ed, zapr\u00ed\u010dinen\u00fdch poruchou v jednej z najd\u00f4le\u017eitej\u0161\u00edch posttransla\u010dn\u00fdch modifik\u00e1ci\u00ed prote\u00ednov \u2013 glykozyl\u00e1cii. V \u013eudskom tele sa<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[290],"tags":[357,649,650],"class_list":["post-1050","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-cdg-en","tag-congenital-disorders-of-glycosylation","tag-glycoconjugates","typ_clanku-review-article"],"acf":{"abstrakt":"<p>Congenital disorders of glycosylation (CDG) is rapidly expanding group of inherited metabolic disorders with various clinical symptoms. A wide range of symptomatology classifies these diseases as difficult to diagnose. Since 2012, a selective screening for CDG, based on isoelectric focusing of serum transferrin, is performed at the Department of Laboratory Medicine, DFNsP Bratislava (Children Faculty Hospital with Policlinics in Bratislava), in the Centre of Inherited Metabolic Disorders. Following a positive result of CDG-screening, close collaboration between clinicians and research scientists from the Centre of Excellence for Glycomics (Institute of Chemistry, Slovak Academy of Sciences) was initiated for further diagnosis of the specific CDG-subtype. This collaboration opens new possibilities for personalized medicine. Structural analysis of N-linked glycans released from serum proteome or released specifically from isolated N- and O-glycobiomarkers by mass spectrometry and whole-exome sequencing of gene panels by next-generation sequencing has thus become available diagnostic techniques that combine clinicians and scientists in intradisciplinary collaborations. Early and accurate diagnosis may help to detect the individuals affected by this group of increasingly expanding inherited metabolic disorders and to understand their molecular bases.<\/p>\n<p><strong>Key words:<\/strong> congenital disorders of glycosylation, CDG, glycoconjugates<\/p>\n","casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"<ul>\r\n \t<li>Pulmonary aspergillosis<\/li>\r\n \t<li>Infections caused by cytomegalovirus \u2013 diagnosis and therapy<\/li>\r\n \t<li>Long-term molecular remission as a precondition for successful pregnancy in patients with chronic myelocyte leukemia<\/li>\r\n \t<li>Chromosome 11 aberrations in a patient with acute myeloid leukemia \u2013 a case study<\/li>\r\n \t<li>New biomarkers in diagnosing IgA nephropathy<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2016-02","to_ping":"","pinged":"","post_modified":"2017-08-16 21:36:48","post_modified_gmt":"2017-08-16 19:36:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2016-02\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"89","upload_clanok":{"ID":1051,"id":1051,"title":"Newslab_2_2016_Kongenit\u00e1lne poruchy glykozyl\u00e1cie","filename":"Newslab_2_2016_Kongenit\u00e1lne-poruchy-glykozyl\u00e1cie.pdf","filesize":503832,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/01\/Newslab_2_2016_Kongenit\u00e1lne-poruchy-glykozyl\u00e1cie.pdf","link":"https:\/\/www.newslab.sk\/en\/congenital-disorders-of-glycosylation-and-their-diagnosis-in-slovakia\/newslab_2_2016_kongenitalne-poruchy-glykozylacie\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2_2016_kongenitalne-poruchy-glykozylacie","status":"inherit","uploaded_to":1050,"date":"2017-02-01 19:41:28","modified":"2017-02-01 19:41:28","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1050","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1050"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1050\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1050"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1050"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1050"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}