Metilmalonska acidurija

master's thesis

• Title (english): Methylmalonic aciduria
• Author: Katarina Šikić
• Mentor: Ivo Barić (mentor)
• Committee member: Irena Senečić-Čala (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

Metilmalonska acidurija je naziv za pojačano izlučivanje metilmalonske kiseline urinom čemu u podlozi može biti skupina rijetkih, autosomno recesivnih bolesti koje nastaju zbog poremećaja u razgradnji aminokiselina razgranatog lanca. Jedna je od najčešćih organskih acidurija. Poremećaj može nastati zbog nedostatne aktivnosti enzima metilmalonil-CoA mutaze (MCM) ili zbog poremećenog metabolizma kobalamina. Posljedično dolazi do nakupljanja metilmalonske kiseline (MMK) i njezinih prekusora koji su odgovorni za simptome bolesti. Klinička slika je nespecifična, može se očitovati od novorođenačke i dojenačke pa do odrasle dobi no najčešće simptomi započinju u prvoj godini života u obliku akutnih metaboličkih kriza. Ukoliko se pravovremeno ne liječe, metaboličke krize mogu dovesti do kome pa i smrti. Dugoročne komplikacije uključuju psihomotoričko zaostajanje, intelektualne poteškoće, bubrežne i razne neurološke te hematološke i imunološke komplikacije. Dijagnostički pristup trebao bi uključivati u prvome redu temeljitu analizu kliničke slike i tijeka bolesti, analizu organskih kiselina u urinu, a zatim za utvrđivanje specifičnog podtipa metilmalonske acidurije (MMA) enzimske analize, prema potrebi s testovima reaktivnosti na kobalamin, te analizu gena. U zemljama u kojima se provodi prošireni novorođenački probir, može i to biti važan element u postavljanju dijagnoze. Dugoročno liječenje usmjereno je na prevenciju metaboličkih kriza. Bolesnici su na niskoproteinskoj dijeti uz dodatak karnitina i kobalamina u onih koji reagiraju na liječenje kobalaminom. U novije vrijeme sve više se spominju transplantacija jetre te kombinirana transplantacija jetre i bubrega za liječenje najtežih slučajeva MMA.

Abstract (english)

Methylmalonic aciduria stands for increased excretion of methylmalonic acid in urine for which the underlying cause can be a group of rare, autosomal recessive disorders of branched-chain amino acid metabolism. It is one of the most common organic acidurias. The defect can be due to the lack of the enzyme methylmalonyl-CoA mutase activity or to defects in cobalamin metabolism. Consequently, there is an accumulation of methylmalonic acid and it's precursors which are responsible for the symptoms of the disease. Clinical presentation is nonspecific, symptoms can occur from neonatal period and infancy up to adulthood, but usually they present in the first year of life in the form of acute metabolic crisis. If the acute crisis is untreated it may progress to coma or death. Long-term complications include developmental delay, intellectual disability, renal complications and various neurological and hematological complications. The diagnostic approach should include a thorough analysis of the clinical presentation and course of the disease in the first place, the analysis of organic acids in the urine, and then the determination of the specific subtype of methylmalonic aciduria by enzymatic analysis, followed by testing cobalamin responsivness and gene analysis. In countries with an expanded newborn screening program it can also be an important element in diagnosis. Long-term management is aimed at preventing metabolic decompensation. Patients are placed on a protein-restricted diet, given carnitine supplements and cobalamin if cobalamin responsive. More recent, liver, or combined kidney-liver transplantation is being talked about as a way of treatment of the most severe cases of methylmalonic aciduria.

• Keywords: metilmalonska acidurija; metilmalonska kiselina; kobalamin; metabolička kriza
• Keywords (english): methylmalonic aciduria; methylmalonic acid; cobalamine; metabolic crisis
• Language: croatian
• URN:NBN: urn:nbn:hr:105:238530
• 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: 2020-02-24 15:48:11