Disorders Of Amino Acid Metabolism Research Articles

Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022

Inborn errors of metabolism (IEMs) are uncommon. Although some studies have explored the distribution and characteristics of IEMs in newborns, the impact of these disorders on hospitalized newborns remains unclear. In this study, we gathered data from 21,840 newborn patients admitted for various medical conditions at the Children’s Hospital of Chongqing Medical University from January 2017 and December 2022. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), and genetic analysis were used to elucidate the disease spectrum, incidence rate, and genetic characteristics of IEMs in hospitalized newborns. The results revealed that the incidence of IEMs in hospitalized newborns was 1/377 (58/21,840), with a higher incidence in full-term infants (1/428) than in premature infants (1/3,120). Among the diagnosed genetic metabolic diseases, organic acid metabolism disorders (1/662), amino acid metabolism disorders (1/950), and fatty acid oxidation disorders (1/10,920) were the most prevalent. Methylmalonic acidemia (MMA), especially the isolated form, emerged as the most common IEM, while neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and ornithine transcarbamylase deficiency (OTCD) were prevalent in premature infants. Of the 58 confirmed cases of IEMs, 72 variants were identified, of which 31.94% (23/72) had not been reported previously. This study contributes to understanding the incidence and clinical features of IEMs in hospitalized newborns, offering more efficient strategies for screening and diagnosing these disorders.

Exploring the “gene–metabolite” network of ischemic stroke with blood stasis and toxin syndrome by integrated transcriptomics and metabolomics strategy

A research model combining a disease and syndrome can provide new ideas for the treatment of ischemic stroke. In the field of traditional Chinese medicine, blood stasis and toxin (BST) syndrome is considered an important syndrome seen in patients with ischemic stroke (IS). However, the biological basis of IS-BST syndrome is currently not well understood. Therefore, this study aimed to explore the biological mechanism of IS-BST syndrome. This study is divided into two parts: (1) establishment of an animal model of ischemic stroke disease and an animal model of BST syndrome in ischemic stroke; (2) use of omics methods to identify differentially expressed genes and metabolites in the models. We used middle cerebral artery occlusion (MCAO) surgery to establish the disease model, and utilized carrageenan combined with active dry yeast and MCAO surgery to construct the IS-BST syndrome model. Next, we used transcriptomics and metabolomics methods to explore the differential genes and metabolites in the disease model and IS-BST syndrome model. It is found that the IS-BST syndrome model exhibited more prominent characteristics of IS disease and syndrome features. Both the disease model and the IS-BST syndrome model share some common biological processes, such as thrombus formation, inflammatory response, purine metabolism, sphingolipid metabolism, and so on. Results of the “gene–metabolite” network revealed that the IS-BST syndrome model exhibited more pronounced features of complement-coagulation cascade reactions and amino acid metabolism disorders. Additionally, the “F2 (thrombin)–NMDAR/glutamate” pathway was coupled with the formation process of the blood stasis and toxin syndrome. This study reveals the intricate mechanism of IS-BST syndrome, offering a successful model for investigating the combination of disease and syndrome.

The correlation between vitamin D3 and arginine metabolism levels in newborns with amino acid metabolism disorders.

This study aimed to explore the correlation between vitamin D3 and arginine (Arg) metabolism indicators in newborns with amino acid metabolism disorders. Based on clinical data, 30 newborns with amino acid metabolism diseases admitted to Shijiazhuang Fourth Hospital from June 2021 to June 2022 were selected as the disease group, and 30 healthy newborns from the same period were selected as the healthy group. After enrollment, blood samples were collected to measure the levels of Arg, Glycine (Gly), and vitamin D3 levels. The levels of Arg metabolism indicators and vitamin D3 levels in the 2 groups and the correlation between vitamin D3 levels and Arg metabolism indicators in the affected group were analyzed. The Arg level in the diseased group was higher than that in the healthy group, whereas the Gly and vitamin D3 levels were lower than those in the healthy group (P < .05). There was a significant negative correlation between vitamin D3 and Arg levels in the affected group, and a significant positive correlation with Gly levels (P < .05). Newborns with amino acid metabolism disorders have abnormally high Arg levels, significantly reduced Gly levels, and significantly decreased vitamin D3 levels. The degree of decline was closely related to the levels of indicators of Arg metabolism. Vitamin D3 supplementation can improve the Arg metabolism status of newborns with amino acid metabolism disorders.

Inherited metabolic disorders in Cyprus

Selective screening for inherited metabolic disorders (IMD) began in Cyprus in 1990. Over the last thirty-three years 7388 patients were investigated for IMD and 200 diagnoses were made (diagnostic yield 2.7%). The existence of a single laboratory of Biochemical Genetics for the whole island facilitated the creation of a national registry for IMD. The minimal prevalence of IMD in Cyprus is 53.3 cases per 100,000 live births. The most common group are disorders of amino acid metabolism (41.0%), followed by disorders of carbohydrate metabolism (16.5%), disorders of complex molecule degradation (16.5%), mitochondrial disorders (10.5%) and disorders of vitamin and co-factor metabolism (5.5%). Hyperphenylalaninaemia is the most common IMD (14.0%) followed by galactosaemia (7.0%), glutaric aciduria type I (5.5%) and MSUD (4.0%). Some disorders were found to have a relatively high incidence in specific communities, for example Sandhoff disease among the Cypriot Maronites and GM1 gangliosidosis in one particular area of the island. Other disorders were found to have a relatively higher overall incidence, compared to other Caucasian populations, for example galactosaemia, glutaric aciduria type I and MSUD, while fatty acid oxidation defects, Gaucher disease and classic PKU were found to have a relatively lower incidence. Molecular characterization of selected disorders revealed many novel genetic variants, specific to the Cypriot population.

Metabolic Characteristics and Discriminative Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature in Preadolescents and Adolescents.

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and even less is known about the study of adolescent SS. In this study, nuclear magnetic resonance (NMR)-based metabolomic analysis combined with least absolute shrinkage and selection operator (LASSO) were performed to identify the biomarkers of different types of SS (including 94 preadolescent GHD (PAG), 61 preadolescent ISS (PAI), 43 adolescent GHD (ADG), and 19 adolescent ISS (ADI)), and the receiver operating characteristic curve (ROC) was further used to evaluate the predictive power of potential biomarkers. The results showed that fourteen, eleven, nine, and fifteen metabolites were identified as the potential biomarkers of PAG, PAI, ADG, and ADI compared with their corresponding controls, respectively. The disturbed metabolic pathways in preadolescent SS were mainly carbohydrate metabolism and lipid metabolism, while disorders of amino acid metabolism played an important role in adolescent SS. The combination of aspartate, ethanolamine, phosphocholine, and trimethylamine was screened out to identify PAI from PAG, and alanine, histidine, isobutyrate, methanol, and phosphocholine gave a high classification accuracy for ADI and ADC. The differences in metabolic characteristics between GHD and ISS in preadolescents and adolescents will contribute to the development of individualized clinical treatments in short stature.

Comparative analysis of inherited metabolic diseases in normal newborns and high-risk children: Insights from a 10-year study in Shanghai

BackgroundCompare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. MethodsData was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. Results232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. ConclusionThere are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.

Targeting glutamate metabolism in chronic lung diseases

AbstractAmino acids are necessary for all life forms, which play various roles. Disorder of amino acid metabolism is now considered an important driving mechanism in diverse pulmonary conditions, particularly chronic lung diseases like chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and lung cancer. Glutamate actively participates in multiple vital biological processes, while the intricate glutamate metabolism, glutamate receptors and glutamate transporters assume crucial regulatory functions in the development of chronic lung diseases. This review aims to discuss the relationship between glutamate dysfunction and chronic lung diseases. By discussing the physiological and pathological function of glutamate, we probe the potential drug targets for chronic lung diseases in the glutamate pathway.

Dietary Adherence in Children with Amino Acid Metabolism Disorders and its Impact on Caregivers’ Quality of Life

This study explored the relationship among socio-demographic factors, patients’ dietary adherence, and the Quality of Life (QoL) experienced by their caregivers. A cross-sectional study was carried out, involving 66 caregivers of pediatric patients in Malaysia diagnosed Amino Acid Metabolism Disorders (AAMDs). Dietary adherence was assessed using a modified version of the Malaysia Medication Adherence Assessment Tool (MyMAAT-12), and the caregiver’s QoL was evaluated using the 36-Item Short Form Survey (SF 36) questionnaire. Majority of the patients were Malay (75.76%), and female (59.1%). Statistical analysis found that caregivers with a higher education level were associated with a higher dietary adherence (rs (64)=0.382, p=0.002) and better mental health (rs (64)=0.281, p=0.022). The age of patients had negative significant correlation with the physical function and general health (rs (64)=0.287, p=0.019) of their caregivers. Besides that, dietary adherence was negatively correlated with social functioning (p=0.010), role limited due to physical health (p=0.018), role limited due to emotional problems (p=0.022), vitality (p=0.021), mental health (p=0.014) and pain (p=0.011). Conclusion: Dietary adherence had a significant impact on the QoL for caregivers of patients with amino acid metabolism disorders. Therefore, it is crucial to explore appropriate treatment strategies and provide support to enhance patients' adherence to their dietary requirements, simultaneously improving the caregivers' QoL.

Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period.

Multi-platform omics sequencing dissects the atlas of plasma-derived exosomes in rats with or without depression-like behavior after traumatic spinal cord injury

BackgroundExosomes can penetrate the blood-brain barrier for material exchange between the peripheral and central nervous systems. Differences in exosome contents could explain the susceptibility of different individuals to depression-like behavior after traumatic spinal cord injury (TSCI). MethodsHierarchical clustering was used to integrate multiple depression-related behavioral outcomes in sham and TSCI rats and ultimately identify non-depressed and depressed rats. The difference in plasma exosome contents between non-depressed and depressed rats after TSCI was assessed in 15 random subjects by performing plasma exosome transcriptomics, mass spectroscope-based proteomics, and non-targeted metabolomics analyses. ResultsThe results revealed that about 27.6% of the rats developed depression-like behavior after TSCI. Totally, 10 differential metabolites, 81 differentially expressed proteins (DEPs), 373 differentially expressed genes (DEGs), and 55 differentially expressed miRNAs (DEmiRNAs) were identified between non-depressed TSCI and sham rats. Meanwhile, 37 differential metabolites, 499 DEPs, 1361 DEGs, and 89 DEmiRNAs were identified between depressed and non-depressed TSCI rats. Enrichment analysis showed that the progression of depression-like behavior after TSCI may be related to amino acid metabolism disorder and dysfunction of multiple signaling pathways, including endocytosis, lipid and atherosclerosis, toll−like receptor, TNF, and PI3K-Akt pathway. ConclusionOverall, our study systematically revealed for the first time the differences in plasma exosome contents between non-depressed and depressed rats after TSCI, which will help broaden our understanding of the complex molecular mechanisms involved in brain functional recombination after TSCI.

Biological agent exerts therapeutic effects by reversing abnormalities in amino acid metabolic pathways in psoriasis.

Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis involving immune system dysregulation and inflammation. Previous studies have indicated that metabolic abnormalities are closely related to the development and occurrence of psoriasis. However, the specific involvement of amino acid metabolism in the pathogenesis of psoriasis remains unclear. In this study, we conducted a comprehensive analysis of amino acid metabolism pathway changes in psoriasis patients using transcriptome data, genome-wide association studies (GWASs) data, and single-cell data. Our findings revealed 11 significant alterations in amino acid metabolism pathways within psoriatic lesions, with notable restorative changes observed after biological therapy. Branched-chain amino acids, tyrosine and arginine metabolism have a causal relationship with the occurrence of psoriasis and may play a crucial role by promoting the proliferation and differentiation of the keratinocytes or immune-related pathways. Activation of phenylalanine, tyrosine and tryptophan biosynthesis suggests a favourable prognosis of psoriasis after treatment. Additionally, we identified the abnormal metabolic pathways in specific cell types and key gene sets that contribute to amino acid metabolic disorders in psoriasis. Overall, our study enhances understanding of the role of metabolism in the pathogenesis of psoriasis and provides potential targets for developing new therapeutic strategies for the disease.

Branched-chain amino acid supplementation drives dynamic changes in gut microbiota without impairing glucose and lipid homeostasis at the different stages of insulin resistance in mice on a high-fat diet

ObjectiveThe potential role of dietary branched-chain amino acids on circulating branched-chain amino acid levels and their relationship with metabolic health are complex, and the literature is inconsistent. We aimed to explore the dynamic effects of branched-chain amino acid supplementation on glucose and lipid homeostasis at different stages of insulin resistance in high-fat diet–fed mice. MethodsMale C57BL/6J mice were fed with a normal chow diet, high-fat diet, or high-fat diet supplemented with 100% branched-chain amino acids for 12 or 24 wk. Metabolic parameters and gut microbiota profiling were performed at these two time points. ResultsHigh-fat diet feeding caused varying degrees of branched-chain amino acid metabolic disorders in two different stages of insulin resistance. Supplementing with branched-chain amino acids further exacerbated branched-chain amino acid accumulation in the early stage of insulin resistance (12 wk), while adding branched-chain amino acids did not further elevate branched-chain amino acid levels in the hyperglycemia and hyperinsulinemia stage (24 wk). Compared with the high-fat diet group, branched-chain amino acid supplementation did not affect body weight; liver total cholesterol and triacylglycerol levels; and serum glucose, insulin, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels as well as glucose tolerance at these two time points but triggered dynamic changes in the gut bacterial diversity and gut microbiota composition and abundance, especially in the genus associated with obesity and related metabolic disorders. ConclusionDietary branched-chain amino acid supplementation drives dynamic changes in circulating branched-chain amino acid levels and gut microbiome without subsequent effects on glucose and lipid homeostasis in high-fat diet–induced obese mice within the parameters of our study.

Synergistic effects of tilapia head protein hydrolysate and walnut protein hydrolysate on the amelioration of cognitive impairment in mice.

Cognitive impairment (CI) is a significant public health concern, and bioactive peptides have shown potential as therapeutic agents. However, information about their synergistic effects on cognitive function is still limited. Here, we investigated the synergistic effects of tilapia head protein hydrolysate (THPH) and walnut protein hydrolysate (WPH) in mitigating CI induced by scopolamine in mice. The results showed that the combined supplementation of THPH and WPH (mass ratio, 1:1) was superior to either individual supplement in enhancing spatial memory and object recognition abilities in CI mice, and significantly lessened brain injury in CI mice by alleviating neuronal damage, reducing oxidative stress and stabilizing the cholinergic system. In addition, the combined supplementation was found to be more conducive to remodeling the gut microbiota structure in CI mice by not only remarkably reducing the ratio of Firmicutes to Bacteroidota, but also specifically enriching the genus Roseburia. On the other hand, the combined supplementation regulated the disorders of sphingolipid and amino acid metabolism in CI mice, particularly upregulating glutathione and histidine metabolism, and displayed a stronger ability to increase the expression of genes and proteins related to the brain-derived neurotrophic factor (BDNF)/TrkB/CrEB signaling pathway in the brain. These findings demonstrate that tilapia head and walnut-derived protein hydrolysates exerted synergistic effects in ameliorating CI, which was achieved through modulation of gut microbiota, serum metabolic pathways and BDNF signaling pathways. © 2024 Society of Chemical Industry.

Определение диагностической значимости маркеров наследственных болезней обмена с применением метода хромато-масс-спектрометрии

Thorough investigation of metabolome by mass spectrometry is of great importance for personalized and preventive medicine. It is only timely laboratory diagnosis involving the use of high-tech chromatographic analysis methods that can help identify the patients with disorders of amino acid and acylcarnitine metabolism. The study was aimed to determine the efficacy of conventional and additional markers of metabolic disorders of amino acids and acylcarnitines detected by chromatography–mass spectrometry for the diagnosis of congenital metabolic disorders in children, as well as to create specific panels of the most effective indicators and determine the potential diagnostic efficacy of indentification of the relationships between the levels of amino acids and acylcarnitines in pediatric patients with congenital metabolic disorders. We assessed amino acid and acylcarnitine profiles in blood spots by high-performance liquid chromatography–tandem mass spectrometry in patients aged 6 months to 16 years (48 boys and 32 girls) with suspected aminoacidopathy and organic aciduria/acidemia. The comparison group consisted of 35 children with suspected peroxisomal metabolic disorders, the control group included 40 generally healthy children of various age groups. The data obtained were used to conduct the analysis of correlations between the groups of markers. Strong correlation was revealed for the levels of metabolically most closely related compounds (r &lt; 0.8, р &lt; 0.001). However, a similar relationship between metabolically not closely related compounds (correlation coefficient 0.45–0.73 (р &lt; 0.001)) was revealed for some groups of compounds. Thus, the acylcarnitine profile can be proposed as an additional potential marker to be used in cases of borderline phenylalanine levels, and the sum of normalized acylcarnitine levels (С12+С16) can be a potential secondary marker of phenylketonuria.

The Association Between Branched-Chain Amino Acid Concentrations and the Risk of Autism Spectrum Disorder in Preschool-Aged Children.

Several studies have linked branched-chain amino acid (BCAA) metabolism disorders with autism spectrum disorder (ASD), but the results have been inconsistent. The purpose of this study was to explore the association between BCAA concentrations and the risk of ASD. A total of 313 participants were recruited from two tertiary referral hospitals from May 2018 to July 2021. Concentrations of BCAAs in dried blood spots were analyzed using liquid chromatography-tandem mass spectrometry-based analysis. Multivariate analyses and restricted cubic spline models were used to identify the association between BCAAs and the risk of ASD, and a nomogram was developed by using multivariate logistic regression and the risk was determined by receiver operating characteristic curve analysis and calibration curve analysis. Concentrations of total BCAA, valine, and leucine/isoleucine were higher in the ASD group, and all of them were positively and non-linearly associated with the risk of ASD even after adjusting for potential confounding factors such as age, gender, body mass index, and concentrations of BCAAs (P < 0.05). The nomogram integrating total BCAA and valine showed a good discriminant AUC value of 0.756 (95% CI 0.676-0.835). The model could yield net benefits across a reasonable range of risk thresholds. In the stratified analysis, the diagnostic ability of the model was more pronounced in children older than 3 years. We provide evidence that increased levels of BCAAs are associated with the risk of ASD, and the nomogram model of BCAAs presented here can serve as a marker for the early diagnosis of ASD.

Branched-chain amino acids promote occurrence and development of cardiovascular disease dependent on triglyceride metabolism via activation of the mTOR/SREBP-1/betatrophin pathway

Branched-chain amino acid (BCAA) metabolism is associated with triglyceride (TG) metabolism and the development of cardiovascular disease (CVD). However, the underlying mechanism remains uncertain. This study included 1302 subjects and followed for 4–5 years. A hyperbranched-chain aminoacidemia rat model was induced by high fructose diet (HFTD). The relationship between BCAAs and TG level and its regulatory mechanism was investigated in vitro. As results, as baseline BCAA percentile increased, subjects had higher prevalence and incidence of T2DM, NAFLD, and CVD risk (P < 0.05). In animal model, the accumulation of BCAAs and TG and betatrophin expression were significantly elevated in the HFTD group when comparing with those in the SD group(P < 0.05). Immunofluorescence and Masson's trichrome staining revealed that the area of interstitial fibrosis was significantly increased in the HFTD group compared with control group. Met treatment significantly decreased TG levels and betatrophin expression and reversed myocardial fibrosis (P < 0.05). In vitro, LO2 cells, stimulated with 0.1–5 mM BCAAs, displayed a significant dose-dependent increase in betatrophin expression (P < 0.05). And 5 mM BCAAs stimulation significantly increased the p-mTOR and SREBP-1 expression (P < 0.05). However, this effect could be reversed by using the corresponding inhibitor or siRNAs. In conclusions, BCAAs promote occurrence and development of cardiovascular disease dependent on TG metabolism via activation of the mTOR/SREBP-1/betatrophin pathway. The study provides a new theory for the pathogenesis of CVD caused by amino acid metabolism disorders.

Hereditary Amino Acid Metabolism Disorders and Urea Cycle Disorders: to Practicing Physician

Hereditary amino acid metabolism disorders (aminoacidopathies) are clinically and genetically heterogeneous group of hereditary metabolic diseases caused by enzymes deficiency involved in amino acid metabolism, that finally leads to progressive damage of central nervous system, liver, kidneys, and other organs and systems. Hereditary urea cycle disorders occur because of enzyme deficiency leading to impaired urea synthesis and hyperammoniemia in patients. The age of disease onset and clinical manifestations severity range from milder, intermittent forms to severe, manifesting in the first hours of life. Expanded neonatal screening (implemented in Russian Federation at 01.01.2023) allows to diagnose diseases from these groups in the first days of life, to prescribe timely pathogenetic therapy. Altogether it helps to prevent the development of disease severe complications. Raising awareness about hereditary aminoacidopathies and urea cycle disorders among pediatricians, neonatologists, neurologists, gastroenterologists, ophthalmologists is a topical issue of modern pediatrics.

Pediatric Cardiomyopathies from the Landscape of Inherited Metabolic Disorders in Southeastern Turkey

Background: Cardiomyopathy (CM) is an important factor affecting inherited metabolic disorders (IMDs). Therefore, documentation of real-world data can increase awareness, and early diagnosis and treatment may improve the outcome. Objectives: The aim of this study was to delineate the underlying etiologies and clinical findings of patients with CM due to IMDs. Methods: In this single-center retrospective study, we aimed to examine the demographic, clinical, and echocardiographic data and prognosis of patients aged 0 - 18 who were diagnosed with CM associated with IMDs between 2010 and 2020. Results: A total of 102 patients were included in the study. Families with consanguineous parents constituted 84.3% of the study population. The mean age of the patients at the time of diagnosis of CM was 26.2 ± 28.2 months. Eighty-six (84.3%) of the patients were diagnosed with hypertrophic CM (HCM), 12 (11.7%) with dilated CM (DCM), and 4 (3.9%) with mixt-type CM. Of the patients, 60 (58.8%) had glycogen storage disease (GSD), 17 (16.6%) had lysosomal storage disorders (LSDs), 11 (10.7%) had fatty acid oxidation disorders, 11 (10.7%) had mitochondrial disorders, and 3 (2.9%) had amino acid and organic acid metabolism disorders. Arrhythmia was detected in 24 patients (23.5%). Fifty-six patients received enzyme replacement therapy (ERT). The echocardiographic parameters of the Pompe patients improved significantly with ERT. The mean follow-up period was 60.9 ± 54.6 months. Thirty-eight (36.1%) of 95 patients with regular follow-up died. Cardiomyopathy type did not affect mortality. Conclusions: Increasingly, cardiac complications have been defined as IMDs. Evaluation should be made in terms of IMDs in unexplained CM and rhythm disorders. On the other hand, patients with certain IMDs should be regularly screened for cardiac complications.

The correlation between serum total bile acid and alanine aminotransferase of pregnant women and the disorders of neonatal hyperbilirubinemia-related amino acid metabolism

BackgroundTo explore the association between liver metabolism-related indicators in maternal serum and neonatal hyperbilirubinemia (NHB), and further investigate the predictive value of these indicators in NHB-related amino acid metabolism disorders.Methods51 NHB and 182 No-NHB newborns and their mothers who treated in the Fourth Hospital of Shijiazhuang from 2018 to 2022 were participated in the study. The differences in clinical data were compared by the Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the relationship between maternal serum indicators and the occurrence of NHB. The correlation analysis and risk factor assessment of maternal serum indicators with NHB-related amino acid metabolic disorders were performed using Spearman correlation analysis and multivariate logistic regression.ResultsCompared to the non NHB group, the NHB group had higher maternal serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, and total bile acid (TBA), while lower levels of serum albumin (ALB), total cholesterol (TC) and high-density lipoprotein (HDL). The levels of alanine (ALA), valine (VAL), ornithine (ORN), and proline (PRO) in the newborns were reduced in NHB group, while arginine (ARG) showed a tendency to be elevated. Multiple logistic regression analysis showed that maternal ALT, AST, ALT/AST, and TBA levels were all at higher risk with the development of NHB, whereas ALB, TC, and HDL levels were negatively associated with NHB development. Increasing maternal TBA level was associated with lower ALA (r=-0.167, p = 0.011), VAL (r=-0.214, p = 0.001), ORN (r=-0.196, p = 0.003), and PRO in the newborns (r=-0.131, p = 0.045). Maternal ALT level was negatively associated with ALA (r=-0.135, p = 0.039), VAL (r=-0.177, p = 0.007), ORN (r=-0.257, p < 0.001), while ALT/AST was positively correlated with ARG (r = 0.133, p = 0.013). After adjustment for confounding factors, maternal serum TBA and ALT were the independent risk factor for neonatal ORN metabolic disorders [(adjusted odds ratio (AOR) = 0.379, 95%CI = 0.188–0.762, p = 0.006), (AOR = 0.441, 95%CI = 0.211–0.922, p = 0.030)]. Maternal ALT level was an independent risk factor for neonatal VAL metabolic disorders (AOR = 0.454, 95%CI = 0.218–0.949, p = 0.036).ConclusionsThe levels of high TBA, ALT, AST, and low HDL, TC of maternal were associated with the risk of NHB. Maternal TBA and ALT levels were independent risk factors for NHB-related amino acid disturbances which have value as predictive makers.

Metabolomic analysis of the serum and urine of rats exposed to diazinon, dimethoate, and cypermethrin alone or in combination

BackgroundMultiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin.MethodsMale Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out.ResultsThe results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys.ConclusionIn summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.