Personalized Genome-Scale Modeling Reveals Metabolic Perturbations in Fibroblasts of Methylmalonic Aciduria Patients.

Cobalamin (vitamin B12) is an essential cofactor for two human enzymes, methionine synthase and methylmalonyl-CoA mutase. Inborn errors of cobalamin metabolism (IECMs) are inherited genetic defects resulting in improper transport, modification, or utilization of cobalamin and include inherited methylmalonic acidurias, a group of IECMs most frequently caused by a defect in the methylmalonyl-CoA mutase enzyme. Here, we performed genome-scale modeling of IECMs to gain insight into their metabolic perturbations.

Steroids and One-Carbon Metabolism: Clinical Implications in Endocrine Disorders.

Background: One-carbon metabolism (OCM) and steroid metabolism are fundamental biochemical pathways that regulate essential cellular processes and physiological functions. OCM is involved in DNA synthesis, methylation, and redox balance, while steroid metabolism governs the production and degradation of steroid hormones, which notably influence growth, reproduction, and stress responses. Despite their distinct roles, emerging evidence suggests a strong interplay between these two pathways.

Exome-based genotype-first reverse phenotyping using structured electronic health record data identifies novel SERPINA1 variants associated with liver markers and demonstrates a dominant effect for specific variants on liver phenotype.

Aim: Although several SERPINA1 genetic variants have been reported for their pathogenicity to induce liver disorders through phenotype-driven approaches, data regarding genotype-driven approaches of the SERPINA1 locus remain unavailable. This study aimed to characterize the clinical and liver biological profiles of patients harboring nonbenign SERPINA1 variants.

Methods: We conducted a retrospective, exome-based genotype-first reverse phenotyping study using structured electronic health record data from consecutive patients from January 1, 2015, to January 31, 2022.

Assessment of Patients With Beta-Lactams Positive Provocation Tests by Biomarkers of IgG-Related Neutrophil Activation.

Background: Beta-lactams (BLs) are the predominant cause of immediate allergic reactions to drugs. Immediate hypersensitivity reactions (IHR) with positive provocation tests and negative skin and in vitro tests have undetermined mechanisms. We evaluated whether biomarkers of IgG-dependent neutrophil activation could help to assess this subgroup of BL IHRs.

A systematic review/meta-analysis of xenobiotics in apple products highlights lack of compliance with European Food Safety Authority Regulation.

Apples and their derivatives are among the most widely consumed fruit products in the world and iconic examples of food-safety issues. By using a systematic search in the PubMed, Web of Science, and Embase databases, we extracted 1374 publications on pesticides, mycotoxins, and heavy metal contents in apple products, which represented 44%, 48%, and 26% of publications on fruit, respectively. We selected 90 articles in which we were able to assess compliance with the European Food Safety Authority's (EFSA) regulations and found a 42.

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus.

: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. : We conducted a scoping review of the literature published in PubMed since January 2003.

Towards personalized genome-scale modeling of inborn errors of metabolism for systems medicine applications.

Inborn errors of metabolism (IEMs) are a group of more than 1000 inherited diseases that are individually rare but have a cumulative global prevalence of 50 per 100,000 births. Recently, it has been recognized that like common diseases, patients with rare diseases can greatly vary in the manifestation and severity of symptoms. Here, we review omics-driven approaches that enable an integrated, holistic view of metabolic phenotypes in IEM patients.

A transgenic mice model of retinopathy of cblG-type inherited disorder of one-carbon metabolism highlights epigenome-wide alterations related to cone photoreceptor cells development and retinal metabolism.

Background: MTR gene encodes the cytoplasmic enzyme methionine synthase, which plays a pivotal role in the methionine cycle of one-carbon metabolism. This cycle holds a significant importance in generating S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the respective universal methyl donor and end-product of epigenetic transmethylation reactions. cblG type of inherited disorders of vitamin B12 metabolism due to mutations in MTR gene exhibits a wide spectrum of symptoms, including a retinopathy unresponsive to conventional therapies.

Epimutation in inherited metabolic disorders: the influence of aberrant transcription in adjacent genes.

Epigenetic diseases can be produced by a stable alteration, called an epimutation, in DNA methylation, in which epigenome alterations are directly involved in the underlying molecular mechanisms of the disease. This review focuses on the epigenetics of two inherited metabolic diseases, epi-cblC, an inherited metabolic disorder of cobalamin (vitamin B) metabolism, and alpha-thalassemia type α-ZF, an inherited disorder of α2-globin synthesis, with a particular interest in the role of aberrant antisense transcription of flanking genes in the generation of epimutations in CpG islands of gene promoters. In both disorders, the epimutation is triggered by an aberrant antisense transcription through the promoter, which produces an H3K36me3 histone mark involved in the recruitment of DNA methyltransferases.

Ocular manifestations in patients with inborn errors of intracellular cobalamin metabolism: a systematic review.

Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes ophthalmological manifestations related to retina, optic nerve and posterior visual alterations, mainly reported in cblC and sporadically in other cbl inborn errors.We searched MEDLINE EMBASE and Cochrane Library, and analyzed articles reporting ocular manifestations in cbl inborn errors.

Causes and consequences of impaired methionine synthase activity in acquired and inherited disorders of vitamin B metabolism.

Methyl-Cobalamin (Cbl) derives from dietary vitamin B and acts as a cofactor of methionine synthase (MS) in mammals. MS encoded by catalyzes the remethylation of homocysteine to generate methionine and tetrahydrofolate, which fuel methionine and cytoplasmic folate cycles, respectively. Methionine is the precursor of S-adenosyl methionine (SAM), the universal methyl donor of transmethylation reactions.

Hypozincemia in the early stage of COVID-19 is associated with an increased risk of severe COVID-19.

Background & Aims: Nutritional predisposition to severe coronavirus disease 2019 (COVID-19) remains unclear. Zinc deficiency could be critical since it is associated with a higher susceptibility to infections. We evaluated the prevalence of hypozincemia in the early stage of COVID-19, its association with risk factors for severe COVID-19 and its prognostic value for hospitalization for respiratory complications within 10 days.

[Newborn screening of phenylketonuria in France].

Phenylketonuria is the most common inborn error of metabolism and causes irreversible mental retardation if left untreated. Its newborn screening was made possible by the technique of blood collection on filter paper developed by Robert Guthrie. Neonatal PKU screening began in France in the early 1970s.