Title Gaucher disease in children
Title (croatian) Gaucherova bolest u djece
Author Ori Zion Shoham
Mentor Mario Ćuk (mentor)
Committee member Ivo Barić (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 2018-07-13, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Pediatrics
Abstract Gaucher disease (GD) is the most common lysosomal storage disease worldwide. The incidence of the disease is significantly higher in certain ethnic groups, such as in Ashkenazi Jews. Mutation in the GBA1 gene results in a decreased catabolic enzymatic activity of the enzyme glucocerebrosidase which leads to the accumulation of glucocerebroside in various organs and their dysfunction. Other genetic mutations at different loci seem to modify the severity of the disease by unclear mechanisms. GD is differentiated into three types. Currently, the common understanding of the disease suggests a spectrum of presentations, ranging from asymptomatic to extremely severe disease rather than three separate entities. Three types of classification of disease are in use, indicating severity and organ system affected in patients.Type 1, known as nonneuropathic, mostly affects the bones, spleen, liver and bone marrow. Type 2 and 3, known as the neuropathic forms of the disease, differing in severity, age of diagnosis, rate of progression and life expectancy. GD2 usually manifests during infancy and has an accelerated progression the results in mortality during 2nd to 4th years of life. Type 3 varies more in presentation and severity. The most common clinical findings in children with GD 1 are hepatosplenomegaly, anemia, and thrombocytopenia. Clinical findings that increase the suspicion for GD require a definitive diagnosis using glucocerebrosidase assay. Before initiation of treatment, a complete baseline assessment is performed to assess severity and to set goals for treatment. The specific treatment for GD in children is enzyme replacement therapy (ERT). This therapy was shown to lower morbidity and complication related to the disease. None of the neuropathic symptoms presenting in GD2 and GD3 seemed to benefit from ERT. These patients will benefit from ERT only in cases of visceral and bone involvement. The follow up of pediatric patients with GD is a lifelong journey that will require regular checks which are essential to assess the efficacy of the treatment and the need for modifications.
Abstract (croatian) Gaucherova bolest (GB) je najčešća lizosomska bolest nakupljanja u svijetu. Učestalost ove bolesti je znatno veća u nekim etničkim skupinama kao što su Židovi Aškenazi. Mutacija u genu GBA1 dovodi do smanjene kataboličke enzimske aktivnosti enzima glukocerebrozidaze koja dovodi do nakupljanja glukocerebrozida u različitim organima i rezultira njihovom disfunkcijom. Mutacije na drugim genskim lokusima, čini se, mijenjaju težinu bolesti putem nejasnih mehanizama. GB se obično dijeli na tri podvrste, ali trenutno razumijevanje bolesti je da se bolest ne sastoji od tri zasebna entiteta, već
zapravo ima spektar prezentacija, od asimptomatskih do teških oblika bolesti. Tri podvrste bolesti se još uvijek često koriste kako bi se označilo koji su organski sustavi pogođeni u određenom pacijentu i koliko teško. Tip 1, poznat kao ne-neuropatski, najčešće utječe na kosti, jetru, slezenu i koštanu srž. Tip 2 i 3 poznatiji su kao neuropatski oblici bolesti i međusobno se razlikuju po težini, dobi dijagnoze i očekivanoj duljini životnog vijeka. GB tip 2 se obično dijagnosticira tijekom prve dvije godine života, a smrt se događa od druge do četvrte godine života. Tip 3 ima varijabilniju kliničku sliku.
Najčešći klinički nalazi kod djece s GB su hepatosplenomegalija, anemija i trombocitopenija. Klinički nalazi koji povećavaju sumnju na GB će zahtijevati konačnu dijagnozu mjerenjem aktivnosti glukocerebrozidaze. Prije započinjanja liječenja obavlja se cjelovita evaluacija kako bi se odredila ozbiljnost bolesti i kako bi se postavili ciljevi liječenja. GB se u djece liječi nadomjesnom enzimatskom terapijom (NET). Pokazalo se da ova terapija smanjuje morbiditet i komplikacije povezane s GB-om. Niti jedan od neuropatskih simptoma koji su bili prisutni u tipovima 2 i 3 GB nije se poboljšao s NETom. Bolesnici s ovim tipovima GB imat će koristi od NET-a samo u slučajevima kad su zahvaćene kosti i visceralni organi. Praćenje pedijatrijskih slučajeva s GB-om je cjeloživotno putovanje koje zahtijeva periodične provjere, potrebne kako bi se procijenila učinkovitost liječenja i potreba za izmjenama istog.
Keywords
Gaucher disease
children
Ashkenazi Jews
diagnosis
treatment
Keywords (croatian)
Gaucherova bolest
djeca
Židovi Aškenazi
dijagnoza
liječenje
Language english
URN:NBN urn:nbn:hr:105:957648
Study programme Title: Medicine (in English language) 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
Terms of use
Public note Pohranitelj objekta unio ključne riječi.
Created on 2019-04-29 11:13:49