Klinička i biokemijska obilježja djece s poremećajima beta-oksidacije masnih kiselina

master's thesis

• Title (english): Clinical and biochemical characteristics of children with fatty acid beta-oxidation disorder
• Author: Stella Mlinarić
• Mentor: Ivo Barić (mentor)
• Committee member: Ivančica Delaš (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Ivo Barić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Mitohondrijski poremećaji β-oksidacije su heterogena skupina prirođenih metaboličkih pogrešaka koje se nasljeđuju autosomno recesivno. Masne kiseline ulaze u proces β-oksidacije, katabolički proces kojim se molekule masnih kiselina razgrađuju kada je mast potrebna kao izvor energije, tijekom razdoblja smanjenog energetskog unosa ili povećanih energijskih potreba. Do sada je opisano osam različitih poremećaja. Ovi poremećaji razlikuju se prema vremenskom nastupu, težini i širokom rasponu... More kliničkih manifestacija, uglavnom povezanih s oštećenjem organa koji imaju povećane metaboličke potrebe. Postoje tri klinička oblika bolesti u svim dobnim skupinama. Neonatalni fenotip je najteži i često po život opasan. Pacijenti obično imaju teška jetrena oštećenja, kardiomiopatiju i mišićnu slabost, a dio pacijenata i encefalopatiju. Infantilni tip javlja se u dojenčadi, ranoj dječjoj ili predškolskoj dobi, s povremenim epizodama letargije, povraćanja, hipoglikemije, disfunkcije jetre, rabdomiolize, srčane slabosti, najčešće povezanim s interkurentnim bolestima. Svi navedeni simptomi ne moraju biti dio svake metaboličke krize. Neki pacijenti godinama mogu biti bez simptoma, iako stalno izloženi riziku od teške metaboličke dekompenzacije i oštećenja organa tijekom bolesti, gladovanja i drugih stresnih stanja. Mišićni tip javlja se kasnije, a obično je praćen mišićnom slabošću, mialgijama, rabdomiolizom te rizikom od oštećenja bubrega. Nakupljanje specifičnih acil-karnitina u krvi i organskih kiselina u urinu karakteristično je za ove poremećaje. Tijekom krize često dolazi do hipoketotične hipoglikemije. Većinom su povećane koncentracije amonijaka, te katalitičke koncentracije kreatin-kinaze i amino-transferaza. Da bi se potvrdila dijagnoza, potrebno je napraviti genetsko testiranje ili mjerenje aktivnosti enzima. Budući da rana dijagnoza i rani početak liječenja poboljšavaju ishode, poremećaji oksidacije masnih kiselina dio su novorođenačkog probira u mnogim zemljama. Less

Abstract (english)

Mitochondrial fatty acid β-oxidation disorders are a heterogeneous group of congenital errors of metabolism that are inherited in an autosomal recessive way. Fatty acids undergo mitochondrial β-oxidation, the catabolic process by which fatty acid molecules are broken down when fat is needed as an energy source, during periods of decreased energy intake or increased energy demands. So far, eight different disorders have been described.
These disorders are characterized by different age... More of onset, severity and a wide variety of clinical manifestations, mostly related to the damage of high metabolic demanding organs. There are three variable clinical forms of disease in all ages. The neonatal phenotype is the most severe, life-threatening presentation of these disorders. Patients usually present with severe hepatopathy, cardiomyopathy and skeletal myopathy, whereas some patients may suffer encephalopathy. The infantile phenotype presents in infancy, early childhood or pre-school age with intermittent episodes of lethargy, vomiting, hypoglycemia, liver dysfunction, rhabdomyolysis and cardiomyopathy, usually associated with intercurrent illnesses. Some patients can be without symptoms for years, although at risk of severe metabolic decompensation and organ damage during illness, fasting and other stressful conditions. The myopathic type presents at a later age, with episodes of muscle weakness, myalgias, rhabdomyolysis, and risk of renal damage. Accumulation of the specific acylcarnitine species in blood and organic acids in urine is characteristic of these disorders. Hypoketotic hypoglycemia often occurs during the crisis. Mostly, elevated levels of ammonia, creatine kinase and aminotransferases are present. To confirm the diagnosis, genetic testing or measurement of enzyme activity should be done. Since early diagnosis and early initiation of treatment are improving outcomes, fatty-acid-oxidation disorders are part of a newborn screening in many countries. Less

• Keywords: beta-oksidacija; acilkarnitin; hipoketotična hipoglikemija; oštećenje organa; novorođenački probir
• Keywords (english): beta-oxidation; acylcarnitine; hypoketotic hypoglycemia; organ damage; newborn screening
• Language: croatian
• URN:NBN: urn:nbn:hr:105:686033
• 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: 2020-01-29 10:34:40