medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2021.10.13-24medgen-1983Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHДиагностическая значимость анализа органических кислот мочи при первичных митохондриальных заболеванияхDiagnostic value of urine organic acids analysis among patients with primary mitochondrial disordersКрыловаТ. Д.KrylovaT. D.tatianadmkrylova@gmail.comКуркинаМ. В.KurkinaM. V.noemail@neicon.ruБарановаП. В.BaranovaP. V.noemail@neicon.ruПырковаЕ. Ю.PyrkovaE. Yu.noemail@neicon.ruЦыганковаП. Г.TsygankovaP. G.noemail@neicon.ruИткисЮ. С.ItkisYu. S.noemail@neicon.ruДоброхотоваЮ. А.DobrohotovaYu. A.noemail@neicon.ruЗахароваЕ. Ю.ZakharovaE. Yu.noemail@neicon.ruФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian Federation20212112202120101324Copyright © Крылова Т.Д., Куркина М.В., Баранова П.В., Пыркова Е.Ю., Цыганкова П.Г., Иткис Ю.С., Доброхотова Ю.А., Захарова Е.Ю., 20212021Крылова Т.Д., Куркина М.В., Баранова П.В., Пыркова Е.Ю., Цыганкова П.Г., Иткис Ю.С., Доброхотова Ю.А., Захарова Е.Ю.Krylova T.D., Kurkina M.V., Baranova P.V., Pyrkova E.Y., Tsygankova P.G., Itkis Y.S., Dobrohotova Y.A., Zakharova E.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/1983

Первичные митохондриальные заболевания (ПМЗ) - генетически и клинически гетерогенные заболевания, характеризующиеся нарушением структуры или функций системы окислительного фосфорилирования (OXPHOS), включая электрон-транспортную цепь. Несмотря на успешное применение методов секвенирования нового поколения в диагностике наследственных заболеваний в последнее десятилетие, существует ряд объективных трудностей в интерпретации результатов, особенно при обнаружении новых генов или новых вариантов нуклеотидной последовательности. Анализ биомаркеров, которые являются индикаторами нарушения функций митохондрий, является важным этапом в диагностике многих ПМЗ. Целью данной работы было проведение анализа спектра и концентраций 72 органических кислот в моче методом газовой хроматографии с масс-спектрометнией (ГХ-МС,7890А/5975С, Agilent Technologies, США) в выборке из 84 пациентов с подтвержденным молекулярно-генетическими методами диагнозом ПМЗ и оценка их диагностической значимости. Среди 84 пациентов с ПМЗ, отклонения в спектре органических кислот были выявлены в 78% (66/84) случаев. Уникальный спектр органических кислот наблюдался при митохондриальных гепатопатиях, связанных с мутациями в гене DGUOK: наравне с повышением уровня лактата, пирувата, 3-гидроксибутирата было выявлено повышение концентрации 4-гидроксифениллактата, 4-гидроксифенилпирувата. При анализе ROC-кривых было показано, что диагностическая значимость маркеров убывает в ряду: 3-гидроксибутират, лактат, пируват. При проведении оценки достоверности теста показано, что повышение концентраций пирувата и 4-гидроксифениллактата может быть принято во внимание при предположении ПМЗ у пациента.

Introduction. Primary mitochondrial disorders (PMD) are a group of clinically and genetically heterogeneous group of diseases characterized by a defective structure and functions of the Oxidative Phosphorylation System (OXPHOS). Despite the advantages of the next generation sequencing, diagnosis of PMD is still challenging. There is no currently available biomarker with high specificity and sensitivity. But the level of metabolites reflecting the defective OXPHOS is needed for making of a diagnosis of PMD. Aim: to reveal the level and spectrum of urine organic acids among patients with confirmed diagnosis (by molecular-genetic analysis) of PMD and to estimate the diagnostic value of the test. Methods. We measured 72 different metabolites in 84 urine samples from patients with PMD by GC-MS (7890А/5975С, Agilent Technologies, USA). Results. In 66/84 cases among the patients, we detected the abnormal level of urine organic acids. We observed a unique spectrum of metabolites in the patients with DGUOK-associated hepatopathy (abnormal levels of lactate, pyruvate, 3-hydroxybutyrate, and at the same time 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate). Using ROC-analysis one of the most informative biomarkers was 3-hydroxybutyrate. But due to the lack of specificity, it could not be classified as a valuable biomarker for PMD. The high level of pyruvate and 4-hydroxyphenyllactate could be taken into account to make a diagnosis of PMD

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The authors declare that there are no conflicts of interest present.