A novel variant associated with an atypical moderate and late-onset LCHAD deficiency.

Background: Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare inherited disease caused by pathogenic variants of gene. Along with signs common to fatty acid oxidation defects (FAOD), specific retina and heart alterations are observed. Because long-chain fatty acid oxidation is selectively affected, supplementations with short/medium-chain fats represent energetic sources bypassing the enzymatic blockade.

Nitrous oxide abuse in the emergency practice, and Review of toxicity mechanisms and potential markers.

Nitrous oxide (NO) toxicity is a concern common to several medical fields. Here, retrospective study of four NO abuses with neurological signs in the emergency practice provides a preliminary basis for a metabolic Discussion/Review. This latter highlights NO abuse as pathology of DNA/RNA/protein methylations, for instance consistent with impairments of protein arginine methyltransferases involved in myelinogenesis and myelopathy in patients.

Undetectable triglycerides related to the combined intake of ascorbic acid and tacrolimus.

Management of triglyceride (TG) levels is essential in intensive care units (ICU), especially to manage the risk of pancreatitis induced by propofol. However, some therapeutics in ICU such as intravenous ascorbic acid protocol, especially used in the context of Covid-19 could lead to false decrease of triglycerides by analytical disruption of Trinder reaction. We report here the case of a sample with unmeasurable triglyceride levels partly due to high plasma ascorbic acid levels.

Citrin deficiency: Does the reactivation of liver aralar-1 come into play and promote HCC development?

Hepatocellular carcinoma (HCC) is a longstanding issue in clinical practice and metabolic research. New clues in better understanding the pathogenesis of HCC might relate to the metabolic context in patients with citrin (aspartate-glutamate carrier 1) deficiency (CD). Because citrin-deficient liver (CDL) is subject to HCC, it represents a unique metabolic model to highlight the mechanisms of HCC promotion, offering different angles of study than the classical metabolic syndrome/obesity/non-alcoholic fatty liver disease (NAFLD)/HCC study axis.

Antioxidants other than vitamin C may be detected by glucose meters: Immediate relevance for patients with disorders targeted by antioxidant therapies.

Owing to their ease of use, glucose meters are frequently used in research and medicine. However, little is known of whether other non-glucose molecules, besides vitamin C, interfere with glucometry. Therefore, we sought to determine whether other antioxidants might behave like vitamin C in causing falsely elevated blood glucose levels, potentially exposing patients to glycemic mismanagement by being administered harmful doses of glucose-lowering drugs.

Plasma BCAA Changes in Patients With NAFLD Are Sex Dependent.

Context: Plasma branched chain amino acid (BCAA) concentrations correlate positively with body mass index (BMI), measures of insulin resistance (IR), and severity of nonalcoholic fatty liver disease (NAFLD). Moreover, plasma BCAA concentrations also differ between the sexes, which display different susceptibilities to cardio-metabolic diseases.

Objective: Assess whether plasma BCAA concentrations associate with NAFLD severity independently of BMI, IR, and sex.

Glucose metabolism and NRF2 coordinate the antioxidant response in melanoma resistant to MAPK inhibitors.

Targeted therapies as BRAF and MEK inhibitor combination have been approved as first-line treatment for BRAF-mutant melanoma. However, disease progression occurs in most of the patients within few months of therapy. Metabolic adaptations have been described in the context of acquired resistance to BRAF inhibitors (BRAFi).

Fluxomic assay-assisted diagnosis orientation in a cohort of 11 patients with myopathic form of CPT2 deficiency.

Carnitine palmitoyltransferase type 2 (CPT2) deficiency, a mitochondrial fatty acid oxidation disorder (MFAOD), is a cause of myopathy in its late clinical presentation. As for other MFAODs, its diagnosis may be evocated when blood acylcarnitine profile is abnormal. However, a lack of abnormalities or specificity in this profile is not exclusive of CPT2 deficiency.

Functional assessment of creatine transporter in control and X-linked SLC6A8-deficient fibroblasts.

Creatine transporter is currently the focus of renewed interest with emerging roles in brain neurotransmission and physiology, and the bioenergetics of cancer metastases. We here report on amendments of a standard creatine uptake assay which might help clinical chemistry laboratories to extend their current range of measurements of creatine and metabolites in body fluids to functional enzyme explorations. In this respect, short incubation times and the use of a stable-isotope-labeled substrate (D-creatine) preceded by a creatine wash-out step from cultured fibroblast cells by removal of fetal bovine serum (rich in creatine) from the incubation medium are recommended.

Association Between Low Plasma Level of Citrulline Before Allogeneic Hematopoietic Cell Transplantation and Severe Gastrointestinal Graft vs Host Disease.

Background & Aims: The gastrointestinal form of acute graft vs host disease increases morbidity and mortality following allogeneic hematopoietic cell transplantation. Plasma levels of citrulline, a non-proteinogenic amino acid, indicate functional enterocyte mass. We measured citrulline in patients before allogeneic hematopoietic cell transplantation and investigated its association with incidence and severity of gastrointestinal graft vs host disease.

Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants.

Background: Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C>T and c.625G>A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics.

A fast method for high resolution oxymetry study of skeletal muscle mitochondrial respiratory chain complexes.

High resolution oxymetry study (HROS) of skeletal muscle usually requires 90-120 min preparative phase (dissection, permeabilization and washing). This work reports on the suitability of a rapid muscle preparation which by-passes this long preparation. For a few seconds only, muscle biopsy from pigs is submitted to gentle homogenization at 8000 rotations per minute using an ultra-dispersor apparatus.

Citrulline and Monocyte-Derived Macrophage Reactivity before Conditioning Predict Acute Graft-versus-Host Disease.

During conditioning, intestinal damage induces microbial translocation which primes macrophage reactivity and leads to donor-derived T cell stimulation. Little is known about the role of intestinal health and macrophage reactivity before conditioning in the development of acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). We assessed (1) citrulline, a surrogate marker of functional enterocyte mass and (2) circulating monocyte-derived macrophage reactivity, before allo-HCT.

Creatine biosynthesis and transport in health and disease.

Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders.

Alteration or adaptation, the two roads for human gastric mucin glycosylation infected by Helicobacter pylori.

Helicobacter pylori is a Gram-negative bacterium that colonizes the mucus niche of the gastric mucosa and infects more than half of the world's human population. Chronic infection may cause gastritis, duodenal ulcer, intestinal metaplasia or gastric cancer. In the stomach, H.

The lacdiNAc-specific adhesin LabA mediates adhesion of Helicobacter pylori to human gastric mucosa.

Adhesion of Helicobacter pylori to the gastric mucosa is a necessary prerequisite for the pathogenesis of H. pylori-related diseases. In this study, we investigated the GalNAcβ1-4GlcNAc motif (also known as N,N'-diacetyllactosediamine [lacdiNAc]) carried by MUC5AC gastric mucins as the target for bacterial binding to the human gastric mucosa.

Creatine and guanidinoacetate reference values in a French population.

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range.

Virulent Shigella flexneri affects secretion, expression, and glycosylation of gel-forming mucins in mucus-producing cells.

Mucin glycoproteins are secreted in large amounts by the intestinal epithelium and constitute an efficient component of innate immune defenses to promote homeostasis and protect against enteric pathogens. In this study, our objective was to investigate how the bacterial enteropathogen Shigella flexneri, which causes bacillary dysentery, copes with the mucin defense barrier. We report that upon in vitro infection of mucin-producing polarized human intestinal epithelial cells, virulent S.

Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent.

Background: The intestinal mucus layer plays a key role in the maintenance of host-microbiota homeostasis. To document the crosstalk between the host and microbiota, we used gnotobiotic models to study the influence of two major commensal bacteria, Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii, on this intestinal mucus layer. B.

Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms.

A population of patients with unexplained neurological symptoms from six major French university hospitals was screened over a 28-month period for primary creatine disorder (PCD). Urine guanidinoacetate (GAA) and creatine:creatinine ratios were measured in a cohort of 6,353 subjects to identify PCD patients and compile their clinical, 1H-MRS, biochemical and molecular data. Six GAMT [N-guanidinoacetatemethyltransferase (EC 2.

Guanidinoacetate methyltransferase (GAMT) deficiency in two Tunisian siblings: clinical and biochemical features.

Background: Guanidinoacetate methyltransferase (GAMT) deficiency is a recently described disorder and few cases have been reported to date. As it is a treatable pathology, we seek to contribute to its better understanding, particularly to further elucidate its biochemical diagnosis for early treatment.

Methods: The patients, two brothers aged 13 years (P1) and 11 years (P2), have been explored for signs and symptoms suggestive of inborn errors of metabolism.