Infantilni oblik Pompeove bolesti

master's thesis

• Title (english): Infantile form of Pompe disease
• Author: Josipa Unić
• Mentor: Mario Ćuk (mentor)
• Committee member: Danko Milošević (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Mario Ćuk (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Pompeova bolest je autosomno recesivna, nasljedna lizosomska bolest nakupljanja koja nastaje posljedično nedostatnoj aktivnosti enzima kisele alfa-glukozidaze. Nedostatak enzima dovodi do nakupljanja glikogena u stanicama srca te skeletnih i glatkih mišića. Ovisno o rezidualnoj aktivnosti enzima i vremenu pojavljivanja simptoma, bolest se dijeli u infantilni, juvenilni i adultni oblik. U infantilnom obliku bolesti, aktivnost enzima je manja od 1% te se bolest poĉinje očitovati intrauterino i u prvim danima života. Ukoliko liječenje ne započne dovoljno rano, završava smrću do kraja prve godine.
Cilj rada je ukazati na važnost ranog dijagnosticiranja i liječenja ove bolesti koje bi omogućilo dulje i kvalitetnije preživljenje oboljelih te donosi preporuke za buduća istraživanja koja bi trebala biti usmjerena na otkrivanje najbolje terapije i mogućnosti njihovog izlječenja.
Klinička slika u infantilnom obliku očituje se brzo nakon rođenja s povećanim srcem, mišićnom slabošću te respiratornim popuštanjem. Dijagnoza se temelji na kliničkoj prezentaciji i mjerenju aktivnosti enzima, a potvrđuje molekularnim testiranjem GAA gena. Ciljano liječenje se provodi humanim rekombinantim enzimom što je dovelo do sporijeg napredovanja bolesti i duljeg preživljavanja oboljelih. Enzimska nadomjesna terapija je sastavljena od sintetizirane bjelančevine te ukoliko pacijenti nemaju aktivnosti vlastitoga enzima, oni razvijaju imunološki odgovor što rezultira nedjelotvornošću terapije. Iz tog se razloga oni dijele na skupinu s malom i one bez ostatne aktivnosti vlastitog enzima, odnosno na CRIM pozitivne i CRIM negativne. Kod CRIM negativnih pacijenata, liječenje započinje istovremenom primjenom imunotolerancijskog potokola s ciljem sprječavanja razvoja imunološke reakcije na terapiju enzimom.

Abstract (english)

Pompe disease is an autosomal - recessively inherited, lysosomal storage disease which results from a deficient activity of the alpha-glucosidaze enzyme. The enzyme deficiency leads to accumulation of glycogen in cardiac, skeletal, and smooth muscle cells. Depending on the degree of residual enzyme activity and age at onset, the disorder is divided into the infantile, juvenile and adult form. In the infantile-onset form of disease, enzyme activity is lower than 1% and the disease starts to present within the intrauterine period and first days of life. If treatment is not started immediately, it has a fatal outcome by the first year of life.
The goal of this study is to highlight the importance of early diagnosis and treatment of the disorder that could provide longer survival and better quality of life to the affected people. It provides recommendations for future research that should be aimed at the best therapy and curing possibilities.
Clinical presentation in the infantile - onset form of disease manifests very soon after birth and include heart enlargement, muscle weakness, and respiratory failure. Diagnosis is based on the clinical presentation and enzyme activity assay, and it is confirmed by molecular testing of the GAA gene. Targeted treatment has been possible since the introduction of the recombinant enzyme and it has provided slower progression of the disease and better outcome in affected patients. Enzyme replacement therapy consists of synthesized protein and if patients have a total absence of their own enzyme, they can develop an immune response which results in therapeutic failure. Because of that, patients are divided into groups with or without any residual activity of the enzyme, and group of CRIM (Cross reactive immunological material) positive and CRIM negative patients, respectively. The CRIM negative group requires the immune tolerance induction protocol before ERT induction in order to prevent an immune response to the enzyme therapy.

• Keywords: Pompeova bolest; kisela alfa-glukozidaza; enzimska nadomjesna terapija
• Keywords (english): Pompe disease; acid alpha - glucosidaze; enzyme replacement therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:553161
• 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: 2017-10-19 10:10:39