Biomarkers for the diagnosis and monitoring of nitrous oxide intoxication: objectives and methodology of the SFBC Working Group.

The recreational use of nitrous oxide (N2O) is an emerging public health issue. Chronic N2O abuse may result in various clinical symptoms, encompassing neurological, psychiatric and cardiovascular outcomes. Despite the difficulties for the laboratory investigation of N2O intoxication, there is currently no guidelines in France to help both clinicians and biologists use appropriate biomarkers for the diagnosis and monitoring of patients with clinical symptoms potentially related to N2O intoxication.

[Review of nutritional components in Covid-19: what about micronutrients?].

Nutritional status is an important protection factor against viral infections. Both undernutrition and malnutrition cause deficits in micronutrients, trace elements and vitamins necessary for various physiological functions and the appropriate functioning of the immune system. These deficiencies and infectious diseases often coexist, with complex interactions.

Adult-onset diagnosis of urea cycle disorders: Results of a French cohort of 71 patients.

Urea cycle disorders (UCD) are rare diseases that usually affect neonates or young children. During decompensations, hyperammonemia is neurotoxic, leading to severe symptoms and even coma and death if not treated rapidly. The aim was to describe a cohort of patients with adult onset of UCDs in a multicentric, retrospective and descriptive study of French adult patients with a diagnosis after 16 years of age of UCDs due to a deficiency in one of the 6 enzymes (arginase, ASL, ASS, CPS1, NAGS, OTC) or the two transporters (ORNT1 or citrin).

Amino acids and vitamins status during continuous renal replacement therapy: An ancillary prospective observational study of a randomised control trial.

Background: Continuous renal replacement therapy (CRRT) is associated with micronutrients loss. Current recommendations are to administer 1-1.5g/kg/day of proteins during CRRT.

Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia.

The cellular receptor Notch1 is a central regulator of T-cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T-cell acute lymphoblastic leukemia (T-ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T-ALL.

Clinical and molecular characterization of adult patients with late-onset MTHFR deficiency.

5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency usually presents as a severe neonatal disease. This study aimed to characterize natural history, biological and molecular data, and response to treatment of patients with late-onset MTHFR deficiency. The patients were identified through the European Network and Registry for Homocystinuria and Methylation Defects and the Adult group of the French Society for Inherited Metabolic Diseases; data were retrospectively colleted.

Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation.

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated.

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.

Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients.

Background: The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients.

Patients And Results: Of the 71 patients, 50 had SUCLA2 mutations and 21 had SUCLG1 mutations.

[Pulmonary embolism in young adults. Think of homocysteine].

Two cases of severe pulmonary embolism in young adults are presented. Biological investigation disclosed hyperhomocysteinemia. This highlights the great interest of homocysteine quantification in such clinical events.

Sight-threatening phenylketonuric encephalopathy in a young adult, reversed by diet.

Phenylketonuria (PKU) leads to severe neurological disorders in childhood, shunned by the diet. The long-term prognosis after diet diversification at adolescence is uncertain. We report a case of cortical blindness in a young patient regressive 1 month after the diet was resumed.

[Acute fatty liver in pregnancy: revealing fetal fatty acid oxidation disorders].

Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome are serious maternal illnesses occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. AFLP may result from mitochondrial defects in the beta-oxidation of fatty acids, in particular a deficiency of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in the fetus. Clinical findings in AFLP vary and its diagnosis is complicated by a significant overlap in clinical and biochemical features with HELLP syndrome.

Hypoketotic hypoglycemia with myolysis and hypoparathyroidism: an unusual association in medium chain acyl-CoA desydrogenase deficiency (MCADD).

Medium-chain acyl-CoA deshydrogenase deficiency (MCADD) is the most frequent disorder of mitochondrial fatty acid oxidation (MFAO). We report a 3 year-old girl with enterovirus viremia who was referred after 36 hours of fasting with hypoketotic hypoglycemic coma and myolysis. Evolution was complicated by acute renal failure, increased serum levels of transaminases and hypoparathyroidism.

Coagulopathies frequency in aseptic osteonecrosis patients.

Many risk factors of aseptic osteonecrosis (AO) are well-known, even if 40% of events are idiopathic. Intravascular thrombosis is one of the physiopathological mechanisms of AO. The aim of this study is to determine the influence of coagulopathies on AO set-up.

Tumoral calcinosis due to GALNT3 C.516-2A >T mutation in a black African family.

Familial Tumoral Calcinosis (FTC) is a rare autosomal recessive disorder of the phosphocalcic metabolism caused by mutations in the FGF23 or GALNT3 genes. We have identified a Beninese family in which two brothers present FTC caused by a homozygous A>T transversion at the acceptor splice site in intron 1 of GALNT3 gene. We report on the clinical, biochemical, histopathological and molecular spectrum of the disorder in this family.

Detection of an intragenic deletion expands the spectrum of CTSC mutations in Papillon-Lefèvre syndrome.

The Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder. The gene responsible for the disease, cathepsin C (CTSC), is localized in 11q14.1-q14.

[Fabry disease: proposed guidelines from a French expert group for its diagnosis, treatment and follow-up].

Fabry disease is a rare and under-recognized disease associated with an altered X-linked gene controlling hydrolase alpha-galactosidase A activity. This mutation impairs the glycosphingolipid metabolism. A multisystemic disease with a highly variable clinical presentation, its principal symptom is acroparesthesia.

A bicistronic SIN-lentiviral vector containing G156A MGMT allows selection and metabolic correction of hematopoietic protoporphyric cell lines.

Background: Erythropoietic protoporphyria (EPP) is an inherited disease characterised by a ferrochelatase (FECH) deficiency, the latest enzyme of the heme biosynthetic pathway, leading to the accumulation of toxic protoporphyrin in the liver, bone marrow and spleen. We have previously shown that a successful gene therapy of a murine model of the disease was possible with lentiviral vectors even in the absence of preselection of corrected cells, but lethal irradiation of the recipient was necessary to obtain an efficient bone marrow engraftment. To overcome a preconditioning regimen, a selective growth advantage has to be conferred to the corrected cells.