Prirođeni poremećaji glikozilacije

master's thesis

• Title (english): Congenital disorders of glycosylation
• Author: Martina Pintarić
• Mentor: Danijela Petković Ramadža (mentor)
• Committee member: Ivo Barić (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Danijela Petković Ramadža (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2022-09-20, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Prirođeni poremećaji glikozilacije su klinički heterogena, brzorastuća skupina nasljednih metaboličkih poremećaja. Glikozilacija je proces posredovan enzimima pri kojem nastaju glikoproteini i glikolipidi unutar staničnih odjeljaka te je jedna od najznačajnijih posttranslacijskih modifikacija proteina. Prirođeni poremećaji glikozilacije se dijele na poremećaje N-glikozilacije, poremećaje O-glikozilacije, kombinirane poremećaje N- i O-glikozilacije te poremećaje glikolipida i biosinteze glikozilfosfatidilinozitolnog sidra. Najbrojniji, a ujedno i najčešći su poremećaji N-glikozilacije. Velika većina poremećaja glikozilacije nasljeđuje se autosomno recesivno i očituje se simptomima zahvaćenosti više organskih sustava. Najčešći simptomi su zaostajanje u razvoju, zastoj u rastu, dismorfija, zahvaćenost neurološkog sustava i jetre, hipotonija, a ponekad i sklonost infekcijama. U dijagnostici se koriste razne metode, a od metoda probira su najvažnije izoelektrično fokusiranje i kapilarna elektroforeza serumskog transferina, tekućinska kromatografija visoke učinkovitosti, tekućinska kromatografija u kombinaciji sa spektrometrijom masa (za poremećaje N-glikozilacije) te izoelektrično fokusiranje serumskog apolipoproteina CIII (za poremećaje O-glikozilacije). Za potvrdu dijagnoze se u većini slučajeva koristi sekvencioniranje nove generacije, metoda molekularne dijagnostike koja je uvelike pridonijela i otkrivanju novih tipova prirođenih poremećaja glikozilacije. Rana i točna dijagnoza ovih bolesti je važna kako bi se što prije pružila adekvatna skrb oboljelima i osiguralo genetsko savjetovanje obitelji. Liječenje se uglavnom temelji na ublažavanju simptoma i sprječavanju daljnjih komplikacija. Etiološko liječenje dostupno je samo za nekoliko tipova prirođenih poremećaja glikozilacije i to u obliku terapije monosaharidima ili kofaktorima, a najuspješnija je primjena manoze u MPI-CDG.

Abstract (english)

Congenital disorders of glycosylation are a clinically heterogeneous, rapidly growing group of inherited metabolic disorders. Glycosylation is an enzyme-mediated process by which glycoproteins and glycolipids are formed in cellular compartments, and it is one of the most significant posttranslational modifications of proteins. Congenital disorders of glycosylation are often divided into disorders of N-glycosylation, disorders of O-glycosylation, combined disorders of N- and O-glycosylation, and disorders of biosynthesis of glycolipids and glycophosphatidylinositol anchor. The most numerous and at the same time the most common disorders are disorders of N-glycosylation. The vast majority of glycosylation disorders are inherited in an autosomal recessive manner and present with symptoms affecting multiple organ systems. The most common symptoms are developmental delay, growth retardation, dysmorphic features, neurologic abnormalities, hepatopathy, hypotonia and sometimes recurrent infections. Various methods are used for diagnosis. The main screening methods are isoelectric focusing and capillary electrophoresis of serum transferrin, high-performance liquid chromatography, liquid chromatography combined with mass spectrometry (for N-glycosylation disorders) and isoelectric focusing of serum apolipoprotein CIII (for O-glycosylation disorders). Next generation sequencing, a molecular diagnostic method that has contributed significantly to the discovery of new types of congenital glycosylation disorders, is commonly used to confirm the diagnosis. Early and accurate diagnosis is important to provide adequate patient management and genetic counseling of family members. Treatment is mainly based on symptom relief and prevention of complications. Etiologic treatment is available only for a few types of congenital glycosylation disorders in the form of therapy with monosaccharides or cofactors, and administration of mannose in MPI-CDG has shown the greatest success.

• Keywords: prirođeni poremećaji glikozilacije; poremećaji N-glikozilacije; poremećaji O-glikozilacije; poremećaji glikozilfosfatidilinozitolnog sidra; multisistemska bolest; PMM2-CDG
• Keywords (english): congenital glycosylation disorders; N-glycosylation disorders; O-glycosylation disorders; glycophosphatidylinositol anchor biosynthesis; multisystemic disease; PMM2-CDG
• Language: croatian
• URN:NBN: urn:nbn:hr:105:272222
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-02-06 12:37:45