Kongenitalne neutropenije u djece

master's thesis

• Title (english): Congenital neutropenias in children
• Author: Maja Pučić
• Mentor: Ernest Bilić (mentor)
• Committee member: Nevena Krnić (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Ernest Bilić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Kongenitalne neutropenije su skupina rijetkih nasljednih bolesti uzrokovanih mutacijama
u genima važnim za proizvodnju, sazrijevanje i otpuštanje neutrofila iz koštane srži.
Očituju se smanjenjem apsolutnog broja neutrofila (ABN) u perifernoj krvi ispod normalnih
vrijednosti i posljedično povećanom učestalošću i težinom infekcija, često već u ranom
djetinjstvu. Najčešći uzrok kongenitalnih neutropenija je autosomno dominantna mutacija
gena ELANE. Zahvaljujući sve većoj dostupnosti različitih metoda genomskog
sekvenciranja, broj mutacija uzročno povezanih s razvojem kongenitalnih neutropenija i
dalje raste. Kongenitalne neutropenije mogu se javiti kao izoliran poremećaj ili kao dio
različitih genetskih bolesti sa širokim spektrom ekstrahematoloških manifestacija. Uz
antibiotike, G-CSF danas predstavlja prvu liniju liječenja pacijenata s kongenitalnom
neutropenijom. Njegova primjena u ovu svrhu značajno je smanjila mortalitet i poboljšala
kvalitetu života pacijenata. Transplantacija hematopoetskih matičnih stanica ostaje
rezervirana za pacijente kod kojih primjena G-CSF-a nije adekvantna ili pacijent ne
pokazuje dostatan odgovor. Alternativne terapijske opcije za specifične podtipove
kongenitalnih neutropenija još traže svoje mjesto u široj primjeni, ali pokazuju obećavajući
potencijal. Zbog povećane učestalosti transformacije u MDS ili AML, mnogi autori
kongenitalne neutropenije smatraju preleukemijskim stanjem. Ta sklonost pripisuje se
stečenim citogenetičkim promjenama i stečenim somatskim mutacijama u različitim
genima od kojih su najbolje poznate mutacije gena CSF3R i RUNX1. Ipak, svi faktori
uključeni u ovaj složeni proces i njihova kompleksna interakcija i dalje su predmet
istraživanja. Većina djece s teškom kongenitalnom neutropenijom i stabilnim
vrijednostima ABN-a danas doživi odraslu dob. Sve veći izbor dijagnostičkih i terapijskih
mogućnosti ulijeva nadu u daljnje poboljšanje ishoda.

Abstract (english)

Congenital neutropenias are a group of rare hereditary diseases caused by mutations in
genes crucial for the production, maturation, and release of neutrophils from the bone
marrow. They manifest as a reduction in the absolute number of neutrophils (ANC) in
peripheral blood below normal values, consequently leading to an increased frequency
and severity of infections, often starting in early childhood. The most common cause of
congenital neutropenias is an autosomal dominant mutation in the ELANE gene. With the
increasing availability of various genomic sequencing methods, the number of mutations
causally linked to the development of congenital neutropenias continues to grow.
Congenital neutropenias can present as isolated disorders or as part of various genetic
diseases with a wide range of extrahematologic manifestations. In addition to antibiotics,
G-CSF currently represents the first line of treatment for patients with congenital
neutropenia. Its use for this purpose has significantly reduced mortality and improved the
quality of life for patients. Hematopoietic stem cell transplantation remains reserved for
patients for whom G-CSF treatment is inadequate or who do not show a sufficient
response. Alternative therapeutic options for specific subtypes of congenital neutropenias
are still seeking broader application but show promising potential. Due to the increased
frequency of transformation into MDS or AML, many authors consider congenital
neutropenias to be pre-leukemic conditions. This tendency is attributed to acquired
cytogenetic changes and somatic mutations in various genes, most notably mutations in
the CSF3R and RUNX1 genes. However, all factors involved in this complex process and
their interactions remain subjects of ongoing research. Most children with severe
congenital neutropenia and stable ANC values reach adulthood today. The growing range
of diagnostic and therapeutic options provides hope for further improvement in outcomes.

• Keywords: kongenitalne neutropenije; učestale infekcije; ELANE mutacija; G-CSF
• Keywords (english): congenital neutropenias; frequent infections; ELANE mutation; G-CSF
• Language: croatian
• URN:NBN: urn:nbn:hr:105:829186
• 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: 2024-07-02 19:43:14