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master's thesis
Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze
Zagreb: University of Zagreb, School of Medicine, 2021. urn:nbn:hr:105:133845
Markusi, Mia
University of Zagreb
School of Medicine
Department of Pediatrics

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

Cite this document

Markusi, M. (2021). Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze (Master's thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:133845

Markusi, Mia. "Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze." Master's thesis, University of Zagreb, School of Medicine, 2021. https://urn.nsk.hr/urn:nbn:hr:105:133845

Markusi, Mia. "Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze." Master's thesis, University of Zagreb, School of Medicine, 2021. https://urn.nsk.hr/urn:nbn:hr:105:133845

Markusi, M. (2021). 'Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze', Master's thesis, University of Zagreb, School of Medicine, accessed 18 April 2024, https://urn.nsk.hr/urn:nbn:hr:105:133845

Markusi M. Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze [Master's thesis]. Zagreb: University of Zagreb, School of Medicine; 2021 [cited 2024 April 18] Available at: https://urn.nsk.hr/urn:nbn:hr:105:133845

M. Markusi, "Kongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze", Master's thesis, University of Zagreb, School of Medicine, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:105:133845

Metadata
TitleKongenitalna adrenalna hiperplazija zbog manjka 21-hidroksilaze
Title (english)Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
AuthorMia Markusi
MentorKatja Dumić Kubat (mentor)
Committee memberNevena Krnić (predsjednik povjerenstva)
Committee memberMarija Jelušić (član povjerenstva)
Committee memberKatja Dumić Kubat (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
(Department of Pediatrics)
Zagreb
Defense date and country2021-07-16, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Pediatrics
Abstract
Kongenitalna adrenalna hiperplazija (KAH) skupina je autosomno recesivnih nasljednih bolesti uzrokovanih mutacijama gena koji kodiraju enzime uključene u sintezu steroidnih hormona u kori nadbubrežnih žlijezda. Učestalost KAH-a iznosi 1:14000 do 1:18000. Najčešći oblik ove bolesti, koji nalazimo u oko 95% bolesnika, nastaje zbog manjka enzima 21-hidroksilaze (21-OH). Gen CYP21A2 kodira enzim 21-hidroksilazu. Fenotip ovih bolesnika vrlo je raznolik i klinička slika varira od gotovo asimptomatske bolesti s blagom hiperandrogenemijom pa sve do teških oblika primarne adrenalne insuficijencije s gubitkom soli i značajnom hiperandrogenemijom. Prema kliničkoj slici i rezultatima biokemijskih i molekularno-genetičkih analiza bolest se pojavljuje u trima oblicima: klasični oblik s gubitkom soli, klasični jednostavni virilizirajući oblik te neklasični oblik. Različite mutacije gena CYP21A2 i njihove kombinacije u ovoj autosomno recesivnoj bolesti za posljedicu imaju različitu rezidualnu aktivnost enzima 21-OH i u skladu s time težinu kliničke slike. Molekularno-genetička analiza potvrđuje dijagnozu, omogućuje genetsko savjetovanje i predviđanje tijeka liječenja. Terapija je ove bolesti supstitucijska, a u djevojčica s virilizacijom i dvosmislenim spolovilom po potrebi i kirurška. Cilj je terapije korekcija manjka kortizola i supresija hiperandrogenemije. Novorođenački se probir za KAH provodi u velikom broju zemalja i omogućuje rano postavljanje dijagnoze KAH-a. Temelji se na određivanju koncentracije 17-OHP iz osušene kapljice krvi na filtar-papiru. Osjetljivije i specifičnije pretrage kao što su LC-MS/MS ili GC-MS koriste se za potvrdu dijagnoze, a omogućuju analizu ciljanih steroidnih hormona. Danas postoji i mogućnost klasične invazivne, ali i neinvazivne prenatalne dijagnostike analizom fetalne DNA iz majčine krvi. Dokazano je da primjena deksametazona tijekom trudnoće majke koja nosi žensko dijete s KAH-om sprječava virilizaciju vanjskog spolovila u fetusa, što je osnova prenatalnog liječenja KAH-a. Međutim, kako se radi o još uvijek nedovoljno istraženom načinu liječenja s nepoznatim dugoročnim učincima na dijete, ovaj oblik terapije nije dio standardne prakse.
Abstract (english)
Congenital adrenal hyperplasia refers to a group of autosomal recessive disorders involving impaired corticosteroid biosynthesis. It affects 1 in 14000 to 18000 newborns. The most common form which affects 95% of patients occurs as a result of 21-hydroxylase deficiency. CYP21A2 gen encodes 21-hydroxylase enzyme. The phenotype is very diverse: clinical features vary from an almost asymptomatic disease with low hyperandrogenemia to severe cases with primary adrenal insufficiency, salt-wasting and severe hyperandrogenemia. Based on the clinical presentation, biochemical and genetic testing CAH has three forms: classic which includes salt-wasting and simple virilizing form and non-classical. Different CYP21A2 mutations and their combinations lead to different levels of 21-OH residual activity and consequently the severity of the clinical presentation. Molecular-genetic testing confirms the diagnosis, enables genetic consulting and anticipates the development of the disease. Treatment is based on replacement therapy and surgical procedures in cases of female patients with virilization and ambiguous genitalia. Therapy goals include achieving adequate levels of cortisol and hyperandrogenemia suppression. Screening tests are performed in various countries because they enable early diagnosis in newborns. The diagnosis is based on the determination of 17-hydroxyprogesterone plasma levels in filter paper blood spots. More sensitive and specific methods such as LC-MS/MS or GC-MS, which enable the analysis of target steroid hormones, are used to confirm the diagnosis. Prenatal diagnosis can be performed with invasive and non-invasive procedures by analyzing fetal DNA from a maternal blood sample. Prenatal treatment is based on the use of dexamethasone if the fetus is female and it has been proven that it prevents external genitalia virilization. Nevertheless, this type of treatment is still controversial because long-term adverse affects are still unknown so it is not included in the standard practice.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:133845
Study programmeTitle: Medicine
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-03-11 09:35:25