Retrospektivna analiza porfirinov izločenih v urin otrok s spektroavtističnimi motnjami

Rojko, Barbara (author), Osredkar, Joško (mentor)

Spektroavtistične motnje (SAM) so razvojno-nevrološke motnje pri katerih opažamo občutne razlike pri spremembah v obnašanju, stereotipnem besednim in nebesednim vedenjem ter zmanjšani sposobnosti socialne interakcije. To pomeni, da je pri osebah, pri katerih se kažejo poteze diagnoze SAM, prisoten poseben in značilen vzorec vedenja in zanimanja za specifične aktivnosti. Etiologija je kompleksna in še vedno ni zadostno pojasnjena, zato vzroke še zmeraj intenzivno preiskujejo. Vse več raziskav se osredotoča na okoljske dejavnike. Izmed okoljskih dejavnikov so glede vplivov pomembne kovine, ki se v telesu pojavljajo kot elementi v sledovih. Med najbolj toksičnimi težkimi kovinami je živo srebro (Hg), ki povzroča različne poškodbe. Hg vpliva na metabolizem hemoglobina in posledično se v urinu pojavljajo različne frakcije porfirinov. Porfirinogeni se izločajo z urinom kot oksidirani porfirini, to sta uroporfirin in koproporfirin. Ključen vzrok za prekomerne vsebnosti porfirinov v človeškem urinu so zapore nekaterih encimskih poti. Težke kovine vplivajo na inhibicijo uroporfirin dekarboksilaze in koproporfirnioksidaze, kar povzroči povečanje koproporfirina in pentakarboksiporfirina v urinu. Prekoproporfirn pa nastaja in vivo iz pentakarboksiporfirinogena pod vplivom težkih kovin (Hg, Pb). V nalogi smo želeli preveriti, ali ima skupina otrok s SAM višje koncentracije celokupnih porfirinov v urinu kot kontrolna skupina otrok. Zanimalo nas je tudi, ali ima podskupina SAM, ki jo opredelimo kot skupino Aspergerjevega sindroma, višje koncentracije celokupnih porfirinov kot ostali SAM. V raziskavo smo vključili 186 otrok, od tega v skupino SAM 102 otroka, v skupino Aspergerjevega sindroma 38 otrok in v kontrolno skupino 46 otrok. Starostni razpon otrok je bil od 2–15 let. Celokupne porfirine v urinu smo določali spektrofotometrično s predhodnim odstranjevanjem interferenc na anionski izmenjevalni koloni. Rezultate smo zaradi lažje interpretacije podali na koncentracijo kreatinina. V skupini s SAM je bila povprečna vrednost celokupnih porfirinov 150,5 µg/g kreatinina (mediana 136,6 µg/g kreatinina), v skupini z Aspergerjevim sindromom 118,1 µg/g kreatinina (mediana 116,1 µg/g) in v kontrolni skupini 58,6 µg/g kreatinina (mediana 36,0 µg/g). Pri primerjavi združene skupine otrok SAM in Aspergerjevega sindroma s kontrolno skupino otrok smo ugotovili, da prihaja do statistično značilnih razlik v koncentracijah celokupnih porfirinov/kreatinina med skupinama (p<0,001). Nadalje smo ugotovili, da pri primerjavi podskupine otrok z Aspergerjevim sindromom in skupine otrok s SAM ni statistično značilnih razlik. Na osnovi rezultatov lahko zaključimo, da je vrednost koncentracij celokupnih porfirinov/kreatinina povišana pri otrocih s SAM. Vzrok je morda v vplivu okolja, vendar bi bilo potrebno analizirati še frakcije porfirinov pri otrocih, ki so imeli povišane vrednosti celokupnih porfirinov.

• Language: Slovenian
• Keywords: spektroavtistične motnje, težke kovine, porfirini
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-116160
• Publication date in RUL: 20.05.2020

Secondary language

• Language: English
• Title: Retrospective analysis of porphyrins in urine of children with autistic spectrum disorders

Abstract

Autism spectrum disorder (ASD) is a form of neurodevelopmental disorder with altered behaviour in the area of social interaction, oral and non-oral communication and stereotypical behaviour. Which means that people with ASD have specific patterns of behavior, interest, and activity that manifest in different ways. The aetiology is complex and to this day rather unexplained and the causes are still intensely researched. More and more research focus on the environmental factors. One of the most important factors is the effects of metals that are found in the body as trace elements. An extremely toxic heavy metal is mercury (Hg), which can cause several damages. Hg affects the haemoglobin metabolism and consequently causes carious porphyrin fractions in the urine. Porphyrinogen are secreted with urine as oxidised porphyrins, such as uroporphyrin and coproporphyrin. Excessive secretion of porphyrins in the urine is a consequence of the blockade of the key enzyme paths. The heavy metals affect the inhibition of the uroporphyrin decarboxylase and coproporphyrin oxidase, which leads to the increase of coproporphyrin and pentacarboxy-porphyrin in the urine. Prekoproporfirn is created in vivo from pentacarboxy-porphyrinogen under the influence of the heavy metals (Hg, Pb). This thesis aims to investigate if a group of children with the ASD has a higher concentration of porphyrins in their urine than the control group of children. The thesis also studies if the ASD subgroup, which is characterised as Asperger syndrome, has increased concentration of porphyrins in their urine in comparison to the group of children with autism spectrum disporder.The study included 186 children, of which 102 were children in the autism spectrum disorder group, and 38 children were in the Asperger syndrome group and 46 children were in the control group. The children were from 2 to 15 years old. Total porphyrins were determined spectrophotometrically by pre-removal of interference on an anion exchange column. The results are presented according to the creatinine concentration for easier interpretation. In the ASD group the average value was 150.5 µg/g creatinine (median value 136.6 µg/g creatinine), the group with Asperger syndrome 118.1 µg/g creatinine (median value 116.1 µg/g creatinine) and the control group 58.6 µg/g creatinine(median value 36.0 µg/gcreatinine). The comparison of the unified groups of the ASD group and the Asperger syndrome group with the control group of children, found that there were statistically significant differences in the concentration results of total porphyrin/creatinine between the groups (p < 0.001). The thesis further finds by comparison of the subgroup of children with Asperger syndrome and the group of children with ASD that there are no statistically significant differences. Based on these results, the researchers came to the following conclusion: the value of total porphyrin/creatinine concentrations is higher in children with ASD. Perhaps the cause can be found in the environment, which cannot be concluded without the analysis of porphyrin fractions with children that had increased values of total porphyrins.

• Keywords: spectroautistic disorder, heavy metals, porphyrins