Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.
- MeSH
- 3-hydroxyacyl-CoA-dehydrogenasy nedostatek MeSH
- acyl-CoA-dehydrogenasa nedostatek MeSH
- dítě MeSH
- hodnocení výsledků zdravotní péče MeSH
- incidence MeSH
- kardiomyopatie diagnóza dietoterapie epidemiologie MeSH
- karnitin analogy a deriváty krev MeSH
- kojenec MeSH
- lidé MeSH
- mitochondriální myopatie diagnóza dietoterapie epidemiologie MeSH
- mitochondriální trifunkční protein nedostatek MeSH
- nemoci nervového systému diagnóza dietoterapie epidemiologie MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- rhabdomyolýza diagnóza dietoterapie epidemiologie MeSH
- stupeň závažnosti nemoci MeSH
- vrozené poruchy metabolismu tuků diagnóza dietoterapie epidemiologie MeSH
- vrozené poruchy metabolismu diagnóza MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
This study tested the hypothesis that in human aging, a decreased intramuscular acylcarnitine status is associated with (pre-)frailty, reduced physical performance, and altered mitochondrial function. We used a cross-sectional study design with well-matched fit and (pre-)frail old males and females, using young males and females as healthy controls. Frailty was assessed according to the Fried criteria and physical performance was determined by 400 m walk test, short physical performance battery and handgrip strength. Muscle and plasma acylcarnitine status, and muscle mitochondrial gene expression was analyzed. Results showed that intramuscular total carnitine levels and short-chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular short-chain acylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. It is, therefore, concluded that in (pre-)frail old females, intramuscular total carnitine levels and short-chain acylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in aging research.
- MeSH
- chůze fyziologie MeSH
- karnitin analogy a deriváty krev chemie metabolismus MeSH
- křehkost metabolismus patofyziologie MeSH
- křehký senior MeSH
- lidé MeSH
- průřezové studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- síla ruky fyziologie MeSH
- stárnutí metabolismus fyziologie MeSH
- svaly metabolismus MeSH
- tělesná výkonnost fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.
- MeSH
- acylkarnitin metabolismus MeSH
- fenylalanin metabolismus MeSH
- glycin-N-methyltransferasa nedostatek metabolismus MeSH
- homocystein metabolismus MeSH
- homocystinurie diagnóza metabolismus MeSH
- karnitin analogy a deriváty metabolismus MeSH
- kyselina methylmalonová metabolismus MeSH
- lidé MeSH
- methionin metabolismus MeSH
- methylentetrahydrofolátreduktasa (NADPH2) nedostatek metabolismus MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- psychotické poruchy diagnóza metabolismus MeSH
- svalová spasticita diagnóza metabolismus MeSH
- vrozené poruchy metabolismu aminokyselin diagnóza metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Plasma profiles of acylcarnitines (ACs) and amino acids (AAs) may have interest as potential biomarkers. Here we analyzed plasma AC and AA profiles in 2 rat models with different metabolic programming outcomes: offspring of dams fed a cafeteria diet during lactation (O-CAF, with a thin-outside-fat-inside phenotype) and the offspring of dams with diet-induced obesity subjected to dietary normalization before gestation [offspring of postcafeteria dams (O-PCaf), nonaltered phenotype]. The purpose was to identify early variables that might indicate a propensity for a dysmetabolic state. O-CAF rats presented higher circulating levels of most of the lipid-derived ACs and higher hepatic expression of genes related to fatty acid oxidation ( Ppara and Cpt1a) than controls [offspring of control dams (O-C)]. They also exhibited an altered plasma AA profile. These differences were not observed in O-PCaf animals. A partial least squares-discriminant analysis score plot of the metabolomics data showed a clear separation between O-CAF and O-C animals. The long-chain ACs (C18, C18:1, C18:2, C16:1, and C16DC) and the AAs glycine, alanine, isoleucine, serine, and proline are the variables mainly influencing this separation. In summary, we have identified a cluster of ACs and AAs whose alterations may indicate poor nutrition during lactation due to maternal unbalanced diet intake and predict the later dysmetabolic phenotype observed in the offspring.-Pomar, C. A., Kuda, O., Kopecky, J., Rombaldova, M., Castro, H., Picó, C., Sánchez, J., Palou, A. Alterations in plasma acylcarnitine and amino acid profiles may indicate poor nutrition during the suckling period due to maternal intake of an unbalanced diet and may predict later metabolic dysfunction.
- MeSH
- aminokyseliny krev MeSH
- dieta * MeSH
- fyziologie výživy v mateřství * MeSH
- játra metabolismus MeSH
- karnitin analogy a deriváty krev MeSH
- kojená zvířata * MeSH
- krysa rodu rattus MeSH
- laktace MeSH
- metabolické nemoci etiologie MeSH
- metabolismus lipidů MeSH
- modely u zvířat MeSH
- multivariační analýza MeSH
- nutriční stav * MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Treatment with all-trans retinoic acid (ATRA), the carboxylic form of vitamin A, lowers body weight in rodents by promoting oxidative metabolism in multiple tissues including white and brown adipose tissues. We aimed to identify novel markers of the metabolic impact of ATRA through targeted blood metabolomics analyses, with a focus on acylcarnitines and amino acids. Blood was obtained from mice treated with a high ATRA dose (50 mg/kg body weight/day, subcutaneous injection) or placebo (controls) during the 4 days preceding collection. LC-MS/MS analyses with a focus on acylcarnitines and amino acids were conducted on plasma and PBMC. Main results showed that, relative to controls, ATRA-treated mice had in plasma: increased levels of carnitine, acetylcarnitine, and longer acylcarnitine species; decreased levels of citrulline, and increased global arginine bioavailability ratio for nitric oxide synthesis; increased levels of creatine, taurine and docosahexaenoic acid; and a decreased n-6/n-3 polyunsaturated fatty acids ratio. While some of these features likely reflect the stimulation of lipid mobilization and oxidation promoted by ATRA treatment systemically, other may also play a causal role underlying ATRA actions. The results connect ATRA to specific nutrition-modulated biochemical pathways, and suggest novel mechanisms of action of vitamin A-derived retinoic acid on metabolic health.
- MeSH
- aminokyseliny krev MeSH
- biologické modely MeSH
- karnitin analogy a deriváty krev MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lipidy krev MeSH
- metabolismus lipidů účinky léků MeSH
- metabolom účinky léků MeSH
- metabolomika * metody MeSH
- myši MeSH
- oxidace-redukce účinky léků MeSH
- stanovení celkové genové exprese MeSH
- tretinoin farmakologie MeSH
- tuková tkáň MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The case of atypical myopathy (AM) in newborn Haflinger foal with clinical signs of depression and weakness appearing 6 hours after birth resulting in recumbency 12 hours after birth is described. The foal's dam was diagnosed with AM in the 6th month of gestation based on clinical signs of a myopathy, elevated serum activity of creatine kinase, metabolomic analysis and the presence of methylenecyclopropyl acetyl carnitine (MCPA-carnitine) in the blood. At the time of delivery, the mare was grazing on a pasture near sycamore trees but was free of clinical signs of AM. Metabolomic analysis of the foal's blood revealed increased concentrations of acylcarnitines and MCPA-carnitine consistent with metabolic profiles of blood from AM affected horses. Two theories could explain this observation (a) hypoglycin A or its metabolites accumulated in the mare's placenta with consequent transfer to fetus or (b) these compounds were secreted into mare's milk.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with multiple clinical faces. Metabolomic profiling studies small molecules present in biological samples by combined use of chromatography with mass spectrometry. OBJECTIVES: The goal of our work was to perform a high performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) metabolomic study to compare the concentrations of metabolites in COPD patients and in controls. MATERIAL AND METHODS: Participants were recruited at the University Hospital, Hradec Králové, Czech Republic, with the approval of the ethics committee. The analysis of blood samples was performed at Health Sciences Center (HSC) in Kuwait. The blood samples were analyzed for concentrations of acylcarnitines and amino acids by high performance liquid chromatography (Waters 2690 HPLC; Waters, Milford, USA) and a triple-quadruple tandem mass spectrometer (Quattro LC, Micromass, Manchester, United Kingdom). RESULTS: Groups of 10 subjects with COPD and 10 healthy controls were analyzed. Carnitine analysis showed that the free carnitine to acylcarnitine ratio (C0/AC ratio) was significantly lower in COPD (0.58 μM/L) compared to the controls (0.73 μM/L; p = 0.002). The mean C8/C2 ratio in the COPD group was significantly higher (0.03 μM/L) - in the control group it was 0 μM/L (p = 0.03). Amino acid analysis showed lower levels of phenylalanine in the COPD group (22.05 μM/L) compared to the controls (30.05 μM/L; p = 0.008). The alanine concentrations were significantly lower in the COPD group (173 μM/L) than in the control group (253 μM/L; p = 0.001). The pyroglutamate levels were higher in COPD (1.58 μM/L) than in the controls (1 μM/L; p = 0.040). CONCLUSIONS: The carnitine and acylcarnitine levels in COPD subjects in this study possibly indicate a predisposition to atherosclerosis as a result of inadequate β-oxidation of fatty acids and show the presence of oxidative stress. Furthermore, the high sensitivity to changes in circulating amino acid levels may allow us to detect subclinical malnutrition and take early preventative interventions such as nutritional supplementation and patient education.
- MeSH
- aminokyseliny krev MeSH
- analýza dat MeSH
- chronická obstrukční plicní nemoc krev metabolismus MeSH
- karnitin analogy a deriváty krev MeSH
- lidé MeSH
- studie případů a kontrol MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
To enable the early diagnosis of pancreatic cancer, the search for and definition of reliable biomarkers remain a subject of great interest, with the specificity and sensitivity of the currently used biomarkers being below the required values. We tested a novel diagnostic approach for pancreatic cancer based on the specific molecular signature of blood plasma components. To acquire more detailed structural information, structure-sensitive chiroptical methods (electronic circular dichroism and Raman optical activity) were supplemented by conventional Raman and infrared spectroscopies. The obtained spectra were subsequently processed by linear discriminant analysis yielding high values of specificity and sensitivity. In addition, to monitor not only large biomolecules as potential biomarkers but also those of low molecular weight, we conducted an analysis of blood plasma samples by using metabolomics. The achieved results suggest a panel of promising biomarkers for a reliable detection of pancreatic cancer.
- MeSH
- cirkulární dichroismus * metody MeSH
- diskriminační analýza MeSH
- karnitin analogy a deriváty krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysofosfatidylcholiny krev MeSH
- metabolomika * metody MeSH
- nádorové biomarkery krev MeSH
- nádory slinivky břišní * krev MeSH
- pilotní projekty MeSH
- Ramanova spektroskopie * metody MeSH
- senioři MeSH
- spektroskopie infračervená s Fourierovou transformací * metody MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- MeSH
- acyl-CoA-dehydrogenasy * genetika krev nedostatek MeSH
- biologické markery MeSH
- dextriny MeSH
- dietoterapie metody MeSH
- dítě MeSH
- hypoglykemie dietoterapie krev MeSH
- karnitin analogy a deriváty krev MeSH
- lidé MeSH
- mutace MeSH
- novorozenecký screening MeSH
- škrob MeSH
- vrozené poruchy metabolismu tuků enzymologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity.
- MeSH
- aminokyseliny krev MeSH
- analýza rozptylu MeSH
- biologické markery MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- fenotyp MeSH
- glukózový toleranční test MeSH
- inzulinová rezistence MeSH
- karnitin analogy a deriváty krev MeSH
- krevní glukóza MeSH
- metabolom MeSH
- metabolomika metody MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- obezita krev diagnóza etiologie MeSH
- porucha glukózové tolerance MeSH
- prognóza MeSH
- shluková analýza MeSH
- tendenční skóre MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH