urine organic acids
Recently Published Documents


TOTAL DOCUMENTS

18
(FIVE YEARS 8)

H-INDEX

5
(FIVE YEARS 1)

2021 ◽  
Vol 8 ◽  
Author(s):  
Baiyu Chen ◽  
Yalan Zhan ◽  
Miriam Kessi ◽  
Shimeng Chen ◽  
Juan Xiong ◽  
...  

Objective: The purpose of this study was to search for differential metabolites in urine organic acids, and to characterize metabolic features that can be used to identify metabolites for exploration of global developmental delay (GDD)/intellectual disability (ID) etiology and pathogenesis.Methods: We screened positive test results that could explain GDD/ID from 1,253 cases, and the major differential metabolites in 132 urine organic acids from the 1,230 cases with negative results (863 GDD cases, 367 ID cases), and 100 typically developing children (TD). Non-supervisory principal component analysis and orthogonal partial least squares discriminant analysis were used to develop models to distinguish GDD/ID from TD children, and to detect major differential metabolites.Results: We get 23 positive results that could identify the cause of GDD/ID from 1253 cases diagnosed with GDD/ID. Among 1,230 negative results, we get the differential metabolites of the GDD group and the ID group had the same trend compared with the TD group. Twenty four differential metabolites were obtained from the GDD group, and 25 from the ID group (VIP > 1.0, p < 0.01). These differential metabolites were mainly related to the following pathways: the synthesis and degradation of ketone bodies, citrate cycle, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, butanoate metabolism, pyruvate metabolism, fatty acid biosynthesis, valine, leucine and isoleucine degradation.Conclusion: The use of metabolomics research methods to detect urine organic acids of children with GDD/ID can discover differential metabolites, which might be valuable for future research on the etiology, pathogenesis, prognosis and possible interventions of GDD/ID. The significantly altered differential metabolites indicators could therefore be potential diagnostic biomarkers for GDD/ID.


Author(s):  
Т.Д. Крылова ◽  
М.В. Куркина ◽  
П.В. Баранова ◽  
Е.Ю. Пыркова ◽  
П.Г. Цыганкова ◽  
...  

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


Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 502
Author(s):  
Dimitris Tsoukalas ◽  
Vassileios Fragoulakis ◽  
Evangelos Papakonstantinou ◽  
Maria Antonaki ◽  
Athanassios Vozikis ◽  
...  

Autoimmune diseases (ADs) are chronic disorders characterized by the loss of self-tolerance, and although being heterogeneous, they share common pathogenic mechanisms. Self-antigens and inflammation markers are established diagnostic tools; however, the metabolic imbalances that underlie ADs are poorly described. The study aimed to employ metabolomics for the detection of disease-related changes in autoimmune diseases that could have predictive value. Quantitative analysis of 28 urine organic acids was performed using Gas Chromatography-Mass Spectrometry in a group of 392 participants. Autoimmune thyroiditis, inflammatory bowel disease, psoriasis and rheumatoid arthritis were the most prevalent autoimmune diseases of the study. Statistically significant differences were observed in the tricarboxylate cycle metabolites, succinate, methylcitrate and malate, the pyroglutamate and 2-hydroxybutyrate from the glutathione cycle and the metabolites methylmalonate, 4-hydroxyphenylpyruvate, 2-hydroxyglutarate and 2-hydroxyisobutyrate between the AD group and the control. Artificial neural networks and Binary logistic regression resulted in the highest predictive accuracy scores (66.7% and 74.9%, respectively), while Methylmalonate, 2-Hydroxyglutarate and 2-hydroxybutyrate were proposed as potential biomarkers for autoimmune diseases. Urine organic acid levels related to the mechanisms of energy production and detoxification were associated with the presence of autoimmune diseases and could be an adjunct tool for early diagnosis and prediction.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 14-14
Author(s):  
Sukyung Chun ◽  
Phil-Kyung Shin ◽  
Myung Sunny Kim ◽  
Min Jung Kim ◽  
Hae-Jeung Lee ◽  
...  

Abstract Objectives Urine organic acids are water-soluble chemical compounds excreted in the urine that are intermediates in many metabolic pathways. Because excess metabolites are excreted in the urine, they may reflect the metabolic status. We investigated whether urine organic acids can determine the metabolic influence of traditional Korean diet (K-diet), a cardiometabolic diet. Methods Fifty two healthy premenopausal women were recruited into a 2 × 2 crossover study with two different diets, K diet and control diet (Westernized current Korean diet). Each diet was provided alternately to all subjects for 1 month with 1 month washout period. Blood and urine samples were collected with anthropometric measurements. Sixty five urine organic acids were measured by LC-MS/MS. Results In the K-diet group, the mean difference of triglyceride (−6.58 ± 4.80 vs −26.35 ± 6.05 mg/dL, P = 0.012), total cholesterol (−12.77 ± 2.78 vs −30.02 ± 2.65 mg/dL, P < 0.001) and LDL- cholesterol (−5.52 ± 2.30 vs −15.88 ± 2.29 mg/dL, P = 0.002) were significantly lower compared to the control group. Body weight and body mass index were also lowered in the K-diet group. Among 65 urine organic acids, TCA cycle associated α-ketoglutarate (21.73 ± 1.27 vs 19.05 ± 1.15 ug/mg creatinine, P = 0.008), malate (1.61 ± 0.10 vs 1.34 ± 0.09, P = 0.008) and isocitrate (22.90 ± 0.68 vs 21.27 ± 0.54, P = 0.014) were lowered in the K-diet group, while citrate (249.16 ± 16.96 vs 324.42 ± 21.18, P = 0.001) and furmarate (0.51 ± 0.03 vs 0.65 ± 0.06, P = 0.029) were elevated in the control group. α-Keto-β-methylvalerate (1.46 ± 0.09 vs 1.09 ± 0.07, P = 0.001), α-ketoisovalerate (0.22 ± 0.02 vs 0.16 ± 0.02, P = 0.012) and methylmalonate (1.30 ± 0.06 vs 1.00 ± 0.06, P < 0.001), which are associated with branched chain amino acid metabolism, were decreased in the K-diet group. Adipate (0.90 ± 0.07 vs 0.65 ± 0.04, P < 0.001) and α-ketoisocaproate (0.46 ± 0.02 vs 0.38 ± 0.02, P = 0.002), which are associated with fatty acid metabolism, were also decreased in the K-diet group. Conclusions K-diet improves clinical parameters and alters urine organic acids associated with TCA cycle and metabolisms of fatty acids and branched-chain amino acid, suggesting that urine organic acids can be useful endpoints to determine the metabolic effects of K-diet and even other diets. Funding Sources Korea Food Research Institute.


2019 ◽  
Vol 5 (1) ◽  
pp. 205511691985389
Author(s):  
George J Nye ◽  
Alison C Major ◽  
Francois X Liebel

Case summary A 14-month-old male castrated domestic shorthair cat, which 2 months prior to presentation underwent hindlimb amputation following a road traffic accident, presented for investigation of four suspected generalised tonic–clonic seizures. Neurological examination was unremarkable. Routine blood work (haematology, biochemistry, ammonia, preprandial bile acids) was unremarkable. MRI of the brain identified marked symmetrical T2-weighted hyperintensities of the cerebellum and brainstem, mainly affecting the grey matter. Urine amino acid and mucopolysaccharide levels were unremarkable. Urine organic acids on two separate samples, 35 days apart, identified highly increased excretion of 2-hydroxyglutaric acid, indicative of 2-hydroxyglutaric aciduria. The cat was started on anticonvulsant therapy with phenobarbitone, which, at the point of writing, has improved seizure control, although the cat has not achieved seizure freedom. Relevance and novel information This case report describes the first reported case of a 2-hydroxyglutaric aciduria, an inherited neurometabolic disorder, as a cause for seizure-like episodes in a cat.


2018 ◽  
Vol 17 (05) ◽  
pp. 191-198
Author(s):  
Ayman Khalil ◽  
Husain Ali Ahmed Malalla ◽  
Husain Naser ◽  
Ahood Almuslamani

AbstractA 10-month-old Bahraini boy born full-term to first-degree cousins, initially had normal developmental milestones, but presented with recurrent encephalopathy and seizures associated with upper respiratory tract infection. With each attack, the patient developmentally regressed further. Brain magnetic resonance imaging showed multiple old and new infarcts. Cerebrospinal fluid biochemistry, microbiology, and amino acids were unremarkable. Tandems mass spectrometry of urine organic acids was unremarkable as well. Electroencephalogram showed asymmetry with cortical irritability. Whole exome sequencing revealed a homozygous mutation of RAN-binding protein 2 gene, suggesting a diagnosis of susceptibility to infection-induced acute encephalopathy 3, which is an autosomal dominant condition. This is the first case to be reported in Bahrain.


2018 ◽  
Vol 62 (3) ◽  
pp. 443-454 ◽  
Author(s):  
Sara Boenzi ◽  
Daria Diodato

Biomarkers are an indicator of biologic or pathogenic processes, whose function is indicating the presence/absence of disease or monitoring disease course and its response to treatment. Since mitochondrial disorders (MDs) can represent a diagnostic challenge for clinicians, due to their clinical and genetic heterogeneity, the identification of easily measurable biomarkers becomes a high priority. Given the complexity of MD, in particular the primary mitochondrial respiratory chain (MRC) diseases due to oxidative phosphorylation (OXPHOS) dysfunction, a reliable single biomarker, relevant for the whole disease group, could be extremely difficult to find, most of times leading the physicians to better consider a ‘biosignature’ for the diagnosis, rather than a single biochemical marker. Serum biomarkers like lactate and pyruvate are largely determined in the diagnostic algorithm of MD, but they are not specific to this group of disorders. The concomitant determination of creatine (Cr), plasma amino acids, and urine organic acids might be helpful to reinforce the biosignature in some cases. In recent studies, serum fibroblast growth factor 21 (sFGF21) and serum growth differentiation factor 15 (sGDF15) appear to be promising molecules in identifying MD. Moreover, new different approaches have been developed to discover new MD biomarkers. This work discusses the most important biomarkers currently used in the diagnosis of MRC diseases, and some approaches under evaluation, discussing both their utility and weaknesses.


Sign in / Sign up

Export Citation Format

Share Document