20.500.12556/RUL-177907 Analiza triptofana in njegovih metabolitov v urinu otrok s spektrom avtističnih motenj Analysis of tryptophan and its metabolites in urine of children with autism spectrum disorders Motnje avtističnega spektra (MAS) predstavljajo skupino kompleksnih nevrorazvojnih motenj, za katere so značilni trajni primanjkljaji v socialni komunikaciji ter omejeni in ponavljajoči se vedenjski vzorci. Kljub številnim raziskavam, etiologija MAS še vedno ni povsem pojasnjena. V zadnjem desetletju se povečuje zanimanje za iskanje novih bioloških označevalcev, ki bi lahko prispevali k zgodnejši diagnostiki in boljšemu razumevanju motenj avtističnega spektra. Med zanimivimi področji preučevanja je presnova triptofana, ki kot esencialna aminokislina sodeluje v treh glavnih presnovnih poteh – serotoninski, kinureninski in indolni – ki povezujejo imunski sistem, črevesno mikrobioto in delovanje možganov. V tem magistrskem delu smo analizirali koncentracije triptofana in njegovih metabolitov v urinu otrok z MAS ter jih primerjali z rezultati zdravih otrok brez nevroloških motenj. Analizo smo izvedli z namenom, da bi ugotovili, ali obstajajo biokemične razlike v presnovi triptofana med otroki z MAS in zdravimi otroki. Dodatno smo preverjali razlike med spoloma znotraj skupine otrok z diagnozo ter povezavo med koncentracijami metabolitov in izraženostjo simptomov glede na lestvico CARS (Childhood Autism Rating Scale). V raziskavo smo vključili 100 otrok, starih od 6 do 17 let, od tega 57 otrok z MAS in 43 zdravih otrok v kontrolni skupini. Analize so bile izvedene na Kliničnem inštitutu za klinično kemijo in biokemijo Univerzitetnega kliničnega centra Ljubljana. Rezultati so pokazali, da imajo otroci z MAS višje mediane presnovkov iz serotoninske in kinureninske poti, predvsem triptofana, kinurenina (KYU) in 5-hidroksiindol-3-ocetne kisline (5-HIAA), medtem ko so imeli zdravi otroci višje mediane indolnih presnovkov, kot so indol-3-ocetna kislina (IAA), indol-3-aldehid (IALD) in indol-3-mlečna kislina (ILA). Statistično značilnih razlik med skupinama nismo potrdili, mejo značilnosti pa je dosegla koncentracija triptofana (p = 0,050). Pri starejših otrocih (nad 11 let) smo opazili značilno višje koncentracije kinurenina in N-acetiltriptofana v skupini otrok z MAS, kar nakazuje na povečano aktivnost kinureninske poti. Primerjava koncentracij metabolitov med spoloma ni pokazala statistično značilnih razlik. Kljub pričakovanju, da bodo koncentracije triptofana in njegovih metabolitov v urinu povezane s stopnjo izraženosti simptomov MAS, se razlike med skupinama glede na CARS oceno niso izkazale za statistično značilne. Rezultati kažejo, da imajo otroci z MAS spremenjeno presnovo triptofana, pri čemer se ta preusmerja iz indolne poti v kinureninsko in serotoninsko pot. Takšne spremembe lahko kažejo na povečano delovanje imunskega sistema ali neravnovesje črevesne mikrobiote. Za bolj zanesljive rezultate in jasnejše ugotovitve bi bilo smiselno raziskavo razširiti na večje število preiskovancev ter vključiti dodatne biološke vzorce, kar bi pomagalo potrditi diagnostični pomen teh metabolitov in poglobiti razumevanje presnovnih procesov, povezanih z MAS. Autism spectrum disorder (ASD) represents a group of complex neurodevelopmental conditions characterized by persistent deficits in social communication and restricted, repetitive patterns of behavior. Despite extensive research, the etiology of ASD is not fully understood. In recent years, there has been growing interest in identifying new biological markers that could contribute to earlier diagnosis and a better understanding of autism spectrum disorders. Among the promising areas of study is tryptophan metabolism, as this essential amino acid participates in three main metabolic pathways – the serotonin, kynurenine, and indole pathways – which connect the immune system, gut microbiota, and brain function. In this master’s thesis, we analyzed the concentrations of tryptophan and its metabolites in the urine of children with ASD and compared them with healthy children without neurological disorders. The purpose of the analysis was to determine whether there are biochemical differences in tryptophan metabolism between children with ASD and healthy controls. Additionally, we examined differences between sexes within the ASD group and explored the relationship between metabolite concentrations and symptom severity based on the Childhood Autism Rating Scale (CARS). The study included 100 children aged 6 to 17 years, of whom 57 had ASD and 43 were healthy controls. Analyses were conducted at the Clinical Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana. The results showed that children with ASD had higher median concentrations of metabolites from the serotonin and kynurenine pathways – particularly tryptophan, kynurenine (KYU), and 5-hydroxyindole-3-acetic acid (5-HIAA) – whereas healthy children had higher median levels of indole metabolites, such as indole-3-acetic acid (IAA), indole-3-aldehyde (IALD), and indole-3-lactic acid (ILA). Although no statistically significant differences were confirmed between the two groups, the concentration of tryptophan reached the threshold of significance (p = 0,050). In older children (over 11 years), significantly higher concentrations of kynurenine and N-acetyltryptophan were observed in the ASD group, suggesting increased activity of the kynurenine pathway. Comparison of metabolite concentrations between sexes showed no statistically significant differences. Despite expectations that urinary tryptophan and metabolite concentrations would correlate with ASD symptom severity, no statistically significant differences were observed between groups based on CARS scores. The findings suggest that children with ASD exhibit altered tryptophan metabolism, characterized by a shift from the indole pathway toward the kynurenine and serotonin pathways. Such changes may indicate increased immune system activity or gut microbiota imbalance. To obtain more reliable and conclusive results, future studies should include a larger number of participants and additional biological samples. This would help confirm the diagnostic relevance of these metabolites and deepen our understanding of the biochemical processes associated with ASD. motnje avtističnega spektra (MAS) presnova triptofana kinureninska pot ocenjevalna lestvica avtizma pri otrocih (CARS) biološki označevalci. autism spectrum disorder (ASD) tryptophan metabolism kynurenine pathway childhood autism rating scale (CARS) biological markers. true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2026-01-13 08:45:05 2026-01-13 08:45:21 2026-01-14 04:26:31 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 124628 31734.pdf 31734.pdf 1 A33836EF5D05FB8928E6230A161A506E b394c4f778d6678db2c76fce13dd63cad8d61134f5ac9d97fd4575d2ddb65f34 c92e0b7d-f053-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225323 Fakulteta za farmacijo 0 0 0