Vanillaktična kiselina i vanilmandelična kiselina - novi biomarkeri u dijagnostici manjka aktivnosti dekarboksilaze aromatskih L-aminokiselina

master's thesis

• Title (english): Vanillactic and vanilmandelic acid - new biomarkers in diagnosics of aromatic L-amino acid decarboxylase deficiency
• Author: Monika Polić
• Mentor: Ksenija Fumić (mentor)
• Committee member: Ksenija Fumić (predsjednik povjerenstva)
• Committee member: Roberta Petlevski (član povjerenstva)
• Committee member: Željka Vogrinc (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2023-01-20, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Manjak aktivnosti dekarboksilaze aromatskih L-aminokiselina rijedak je autosomno-recesivni poremećaj koji
dovodi do teškog deficita kateholamina i serotonina. Klinička slika uključuje različite stupnjeve neuroloških oštećenja,
uključujući motoričke i neuromotoričke simptome. Uspješnost liječenja ovisi o pravovremenom postavljanju dijagnoze
i početku terapije. Postavljanje dijagnoze manjka aktivnosti AADC temelji se na određivanju koncentracije
neurotransmitera u likvoru i molekularnoj dijagnostici zbog čega se bolesnici izlažu invazivnom postupku uzimanja
uzoraka za analizu. Vanillaktat (VLA), vanilmandelična kiselina (VMA) i njihov omjer VLA/VMA mogu se
analizirati u sklopu rutinske analize organskih kiselina u urinu i smatraju se potencijalnim neinvazivnim biokemijskim
biljezima u postavljanju dijagnoze AADC. Cilj ovog diplomskog rada bio je odrediti referentne intervale za VLA,
VMA i njihova omjera VLA/VMA u urinu retrospektivnom analizom organskih kiselina bolesnika suspektnih na
neurometaboličke poremećaje. 219 obrađenih bolesnika podijeljeno je u tri dobne skupine, a uzorci su analizirani inhouse
metodom ekstrakcije organskih kiselina na sustavu za plinsku kromatografiju s masenom spektrometrijom. Kao
dodatni marker korišten je N-acetiltirozin. Određivanje referentnih intervala VLA, VMA i VLA/VMA u urinu u
sklopu rutinske analize organskih kiselina može pomoći u diferencijalnoj dijagnostici neurometaboličkih bolesti.

Abstract (english)

Aromatic L-amino acid decarboxylase deficiency is rare autosomal recessive disorder that leads to severe deficit
of catecholamine and serotonin. The clinical picture includes varying degree of neurological damage, including motor
and neuromotor symptoms. Treatment outcomes depends on the timepoint when therapy started. Key diagnostic test
for AADC confirmation are measurement neurotransmiters in cerebrospinal fluid and genetic testing. However, to
perform this testing, patients are exposed to intensive lumbar puncture procedure. Determination of vanillactic acid
(VLA), vanillylmandelic acid (VMA) and VLA/VMA ratio as part of organic acid analysis in urine is considered a
reliable approach using non-invasive biomarkers in the diagnosis of AADC. The aim of this thesis was to determine
reference intervals of VLA, VMA and VLA/VMA ratio in urine. Retrospective analysis of urinary organic acids
obtained from 219 patients suspected for neurometabolic disorders were included in this study. Patients were divided
into groups depending on age. Organic acids in urine were measured using in-house method by gas-chromatography
mass spectrometry. As additional biomarker, N-acetyltyrosine was used. Determination of reference intervals of VLA,
VMA and VLA/VMA ratio as a part of organic acids analysis in urine may help to differentiate neurometabolic
patients with possible AADC deficiency from other neurometabolic disorders.

• Keywords: dekarboksilaza aromatskih L-aminokiselina; AADC; vanilaktična kiselina; vanilmandelična kiselina; nasljedni metabolički poremećaj
• Keywords (english): aromatic L-amino acid decarboxylase; AADC; vanillactic acid; vanilmandelic acid
• Language: croatian
• URN:NBN: urn:nbn:hr:163:649496
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-02-02 12:20:14