Selective screening of metabolic diseases in Estonia: the application of new diagnostic methods
Date
2012-05-29
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Abstract
Pärilike energiatootmisega seotud haiguste – rasvhapete oksüdatsiooni defektide ja mitokondriaalste haigustega, on seotud energiasõltuvate organite (aju, lihased, maks) kahjustumine, märkimisväärne elukvaliteedi langus ja suur suremus imiku- ja väikelapseeas. Käesolev uurimistöö käsitleb uute meetodite rakendamist nende haiguste haiguste diagnostikas Eesti tingimustes. Määratakse ka nende haiguste levimust Eestis. Lisaks kirjeldatakse mehhanisme, mis mõjutavad harvaesinevate haigusvormide avaldumist kolmandat tüüpi päriliku ainevahetushaiguse – ornitiintranskarbamülaasi defitsiidiga naissoost indiviidil.
Rasvhappeid transporditakse organismis karnitiini estritena. Sellest lähtuvalt rakendati esmakordselt Eestis kliinilisse praktikasse karnitiini estrite analüüs, mis võimaldab ühel mõõtmisel iseloomustada kõigi erinevate rasvhapete metabolismi. Kõige sagedamini esinev rasvhapete oksüdatsiooni defekt Eestis on pika ahelaga hüdroksü-atsüülkoensüüm A defitsiit, esinemissagedusega 1:91,670 vastsündinu kohta. Mitokondriaalse energiatootmise häirete diagnostikas hinnati eelnevalt väljatöötatud diagnostilise algoritmi kliinilist efektiivsust. Uuringusse suunati patsiendid regionaalsete haiglate vastsündinute, laste närvihaiguste ja üldpediaatria osakondadest vastavalt näidustusele. Tulemustest järeldub, et kasutatud algoritm võimaldab diagnoosida enamiku vastsündinu- ja imikueas avalduvaid haigusjuhte. Mitokondriaalsete haiguste esinemissagedus Eestis on 1:20,746 elussünni kohta. Uute diagnostikameetodite kasutusele võtmine võimaldab asjakohase ravi diagnoositud patsientidele ning võib olla elupäästev.
Ornitiintranskarbamülaasi defitsiidile viitavate sümptomiga tüdruku geneetiliste uuringute tulemused võimaldasid järeldada, et haiguse avaldumisel antud indiviidil mängivad rolli erinevad mehhanismid. Seda võib mõjutada X-kromosoomi osa puudumine ning vigase kromosoomi kasutamine võib olla erinev erinevates kudedes ning eluetappides.
Current study focuses on application of new methods into the diagnostics of metabolic disorders affecting energy production, like fatty acid oxidation disorders and mitochondrial diseases in Estonia. These disorders affect organs with large energy consumption (brain, muscle, liver) and are related to significant mortality. The frequency on those disorders in Estonia is estimated. Additionaly, the mechanisms underlying the rare presentation of X-linked ressecive disorder (ornithine transcarbalylase deficiency) in female are studied. Fatty acids are transported in organism as carnitine esters. Therefore the method of analysis of carnitine esters was introduced, which allows to characterize the metabolism of all fatty acids in the single analysis. The long-chain hydroxyacyl-CoA dehydrogenase deficiency is the most prevalent fatty acid oxidation defect in Estonia with the prevalence of 1:91,670. In the diagnostics of mitochondrial disorders the effectiveness of previously established diagnostic algorithm was evaluated. Patients from the neonatology, children neurolology and pediatric departmets from the regional hospitals of Estonia were recruited.Our algorithm for identifying patients with mitochondrial disease is informative in the vast majority of neonatal and infantile onset of cases. The live-birth prevalence for mitochondrial disorders according to this study is 1 per 20,764 live births. The application of the new diagnostic methods enables accurate treatment for patients with rare metabolic disease and can be life-saving. In the female patient with some symptoms of ornithine transcarbalylase deficiency, complex mechanisms like large deletions on X-chromosome, skewing of X-inactivation in different tissues and ages contribute to the clinical manifestation.
Current study focuses on application of new methods into the diagnostics of metabolic disorders affecting energy production, like fatty acid oxidation disorders and mitochondrial diseases in Estonia. These disorders affect organs with large energy consumption (brain, muscle, liver) and are related to significant mortality. The frequency on those disorders in Estonia is estimated. Additionaly, the mechanisms underlying the rare presentation of X-linked ressecive disorder (ornithine transcarbalylase deficiency) in female are studied. Fatty acids are transported in organism as carnitine esters. Therefore the method of analysis of carnitine esters was introduced, which allows to characterize the metabolism of all fatty acids in the single analysis. The long-chain hydroxyacyl-CoA dehydrogenase deficiency is the most prevalent fatty acid oxidation defect in Estonia with the prevalence of 1:91,670. In the diagnostics of mitochondrial disorders the effectiveness of previously established diagnostic algorithm was evaluated. Patients from the neonatology, children neurolology and pediatric departmets from the regional hospitals of Estonia were recruited.Our algorithm for identifying patients with mitochondrial disease is informative in the vast majority of neonatal and infantile onset of cases. The live-birth prevalence for mitochondrial disorders according to this study is 1 per 20,764 live births. The application of the new diagnostic methods enables accurate treatment for patients with rare metabolic disease and can be life-saving. In the female patient with some symptoms of ornithine transcarbalylase deficiency, complex mechanisms like large deletions on X-chromosome, skewing of X-inactivation in different tissues and ages contribute to the clinical manifestation.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone.
Keywords
ainevahetushäired, lipiidide ainevahetus, pärilikud haigused, sõeluuringud, Eesti, metabolic disease, fat metabolism, hereditary diseases, screening, Estonia