45,114 results match your criteria errors metabolism

[Hyperammonaemic encephalopathy in adults without liver diseases].

Ugeskr Laeger 2021 Mar;183(13)

Hyperammonaemic encephalopathy (HAE) in adults in the absence of acute or chronic liver disease is a severe condition caused by inborn errors of metabolism or acquired conditions like bariatric surgery, medications or malignancy as summarised in this review. Metabolic defects are most often caused by partial defects in the urea cycle enzymes demasked by stressors, whereas mechanisms underlying the acquired causes are complex and often multifactorial. Awareness of HAE and knowledge of the causes can help the clinician to deal appropriately with patients presenting with symptoms suggesting HAE and no signs of liver disease. Read More

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Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta.

Arterioscler Thromb Vasc Biol 2021 Apr 8:ATVBAHA120315587. Epub 2021 Apr 8.

UMR Inserm 1256 N-GERE (Nutrition, Génetique et Exposition aux Risques Environmentaux) (B.B., S.H., R.-M.G.-R., J.-L.G.).

Objective: Deficiency in vitamin B12/folate (methyl donor deficiency [MDD]) produces cardiovascular outcomes during aging and fetal programming effects in newborns of MDD mothers. Whether fetal programming provokes long-term effects on aorta remains largely unknown. Approach and Results: We investigated the impact of fetal programming on ascending aorta of aged rats born from mothers subjected to MDD during gestation/lactation. Read More

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Familial hyperphosphatemic tumoral calcinosis in an unusual and usual sites and dramatic improvement with the treatment of acetazolamide, sevelamer and topical sodium thiosulfate.

J Pediatr Endocrinol Metab 2021 Apr 6. Epub 2021 Apr 6.

Department of Inborn Errors of Metabolism, Faculty of Medicine, Gazi University, Ankara, Turkey.

Objectives: Familial hyperphosphatemic tumoral calcinosis is a rare disorder characterized by hyperphosphatemia with recurrent ectopic periarticular calcifications, in addition to other visceral and vascular manifestations, without any inflammatory or neoplastic disorder. The available treatment strategies are limited. Here we report an eight year old female patient with recurrent lesions under the chin, and bilateral hips which are painful and improving of the size of the lesions and hyperphosphatemia. Read More

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Two patients from Turkey with a novel variant in the gene and review of the literature.

J Pediatr Endocrinol Metab 2021 Apr 6. Epub 2021 Apr 6.

Deparment of Pediatric Metabolism and Nutrition, Gazi University School of Medicine, Çankaya, Ankara, Turkey.

Objectives: GM2 gangliosidosis is a rare form of inborn errors of metabolism including Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency. GM2 activator protein deficiency is an ultra-rare form of GM2 gangliosidosis. To date, 16 cases of GM2 activator protein deficiency have been reported in the literature, and among them, 11 cases were the infantile form of the disease. Read More

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Plasma Phospholipidomic Profile Differs between Children with Phenylketonuria and Healthy Children.

J Proteome Res 2021 Apr 5. Epub 2021 Apr 5.

Mass Spectrometry Center, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.

Phenylketonuria (PKU) is a disease of the catabolism of phenylalanine (Phe), caused by an impaired function of the enzyme phenylalanine hydroxylase. Therapeutics is based on the restriction of Phe intake, which mostly requires a modification of the diet. Dietary restrictions can lead to imbalances in specific nutrients, including lipids. Read More

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Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients' Lives, and Reduce Costs.

Nanomaterials (Basel) 2021 Mar 16;11(3). Epub 2021 Mar 16.

Department of Biology and Biotechnology "C. Darwin", University of Rome Sapienza, 00185 Rome, Italy.

Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients' lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Read More

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Neonatal Urine Screening Program in the Province of Quebec: Technological Upgrade from Thin Layer Chromatography to Tandem Mass Spectrometry.

Int J Neonatal Screen 2021 Mar 20;7(1). Epub 2021 Mar 20.

Division of Medical Genetics, Department of Pediatrics, Centre de Recherche-CHUS, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

The Quebec Neonatal Urine Screening Program was initiated in 1971 with overall screening inception of newborns in 1973. Forty-seven years later, over 3.5 million babies have been screened for up to 25 inborn errors of metabolism divided into two groups: (1) urea cycle disorders and organic acidurias; and (2) disorders of amino acid metabolism and transport. Read More

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β3-Adrenoreceptors as ROS Balancer in Hematopoietic Stem Cell Transplantation.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Division of Pediatric Oncology/Hematology, Meyer University Children's Hospital, 50139 Florence, Italy.

In the last decades, the therapeutic potential of hematopoietic stem cell transplantation (HSCT) has acquired a primary role in the management of a broad spectrum of diseases including cancer, hematologic conditions, immune system dysregulations, and inborn errors of metabolism. The different types of HSCT, autologous and allogeneic, include risks of severe complications including acute and chronic graft-versus-host disease (GvHD) complications, hepatic veno-occlusive disease, lung injury, and infections. Despite being a dangerous procedure, it improved patient survival. Read More

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Opportunities and challenges for the computational interpretation of rare variation in clinically important genes.

Am J Hum Genet 2021 Apr;108(4):535-548

Departments of Bioengineering & Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address:

Genome sequencing is enabling precision medicine-tailoring treatment to the unique constellation of variants in an individual's genome. The impact of recurrent pathogenic variants is often understood, however there is a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequential variants and associated mechanisms. Read More

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Redox-Linked Coordination Chemistry Directs Vitamin B Trafficking.

Acc Chem Res 2021 Apr 2. Epub 2021 Apr 2.

Department of Biological Chemistry, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.

ConspectusMetals are partners for an estimated one-third of the proteome and vary in complexity from mononuclear centers to organometallic cofactors. Vitamin B or cobalamin represents the epitome of this complexity and is the product of an assembly line comprising some 30 enzymes. Unable to biosynthesize cobalamin, mammals rely on dietary provision of this essential cofactor, which is needed by just two enzymes, one each in the cytoplasm (methionine synthase) and the mitochondrion (methylmalonyl-CoA mutase). Read More

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Overestimation of 3α- over 3β25-Hydroxyvitamin D Levels in Serum: A Mechanistic Rationale for the Different Mass Spectral Properties of the Vitamin D Epimers.

J Am Soc Mass Spectrom 2021 Apr 29;32(4):1116-1125. Epub 2021 Mar 29.

Department of Chemistry, Humboldt University Berlin, 12489 Berlin, Germany.

The metabolism of vitamin D includes a parallel C-3 epimerization pathway-in addition to the standard metabolic processes for vitamin D-reversing the stereochemical configuration of the -OH group at carbon-3 (β→α). While the biological function of the 3α epimer has not been elucidated yet, the additional species cannot be neglected in the analytical determination of vitamin D, as it has the potential to introduce analytical errors if not properly accounted for. Recently, some inconsistent mass spectral behavior was seen for the 25-hydroxyvitamin D (25(OH)D) epimers during quantification using electrospray LC-MS/MS. Read More

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Use of therapeutic outcomes monitoring method for performing of pharmaceutical care in oncology patients.

J Oncol Pharm Pract 2021 Mar 27:10781552211005072. Epub 2021 Mar 27.

Pharmacy and Pharmaceutical Administration Department, College of Pharmacy, Federal Fluminense University, Niterói, RJ, Brazil.

This study aimed to implement pharmaceutical care using the therapeutic outcome monitoring (TOM) method for pharmacotherapeutic follow-up of oncological patients. This was a prospective longitudinal study involving patients undergoing oral chemotherapy. The study environment was an outpatient pharmacy at a tertiary-level oncology hospital. Read More

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Clinical and biochemical footprints of inherited metabolic disease. V. Cerebral palsy phenotypes.

Mol Genet Metab 2021 Mar 13. Epub 2021 Mar 13.

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Cerebral palsy is the most common physical disability of childhood describing a heterogeneous group of neurodevelopmental disorders that cause activity limitation, but often are accompanied by disturbances of sensation, perception, cognition, communication and behavior, or by epilepsy. Inborn errors of metabolism have been reported in the literature as presenting with features of cerebral palsy. We reviewed and updated the list of metabolic disorders known to be associated with symptoms suggestive of cerebral palsy and found more than 150 relevant IEMs. Read More

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Increasing the spectrum of white matter diseases with tigroid pattern on MRI: glutaric aciduria type 1 - case report.

BMC Pediatr 2021 Mar 27;21(1):146. Epub 2021 Mar 27.

Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland.

Background: Most white matter diseases present on magnetic resonance imaging as focal or diffuse T2-hyperintensities. However, in a few of them, radially oriented stripes of low (relatively normal) signal intensity are observed within diffusely affected T2-hyperintense cerebral white matter and are called "tigroid pattern" in the literature. The fornix is a tiny white matter fibers bundle playing crucial role in cognitive functioning, easily overlooked on magnetic resonance imaging and not described in inborn errors of metabolism. Read More

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Rapid Detection and Treatment of Inborn Errors of Metabolism in the Newborn Period: Beginning of a New Trend.

Indian J Pediatr 2021 Mar 26. Epub 2021 Mar 26.

Institute of Medical Genetics & Genomics, Sir Ganga Ram Hospital, New Delhi, 110060, India.

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The Urine Anion Gap: Common Misconceptions.

J Am Soc Nephrol 2021 Mar 5. Epub 2021 Mar 5.

Renal Division, Department of Medicine, State University of New York at Downstate, Brooklyn, New York.

Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Read More

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[Clinical and molecular genetic analysis of a case of MEGDEL syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Mar;38(3):271-274

Shanxi Rehabilitation Research Center, Taiyuan, Shanxi 030000, China.

Objective: To explore the clinical and genetic characteristics of a child with MEGDEL syndrome.

Methods: Clinical data of the child was reviewed. Peripheral blood samples of the child and his parents were collected. Read More

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Newborn screening in Latin America: A brief overview of the state of the art.

Am J Med Genet C Semin Med Genet 2021 Mar 22. Epub 2021 Mar 22.

Detección de Errores Congénitos, Fundación Bioquímica Argentina, La Plata, Argentina.

Latin America is a region consisting of 20 countries that present a wide diversity in terms of a geographic area as well as demographics, ethnicity, economy, social, and healthcare systems. This diversity also applies to the newborn screening (NBS) activities, as demonstrated by the start dates and modalities of implementation as organized programs, the panel of diseases screened for, the available technologies for testing, the coverage, the legislation in force, and the degree of development and success reached. Based on these characteristics, Latin American countries can currently be classified into five groups ranging from fully established national programs to no program at all. Read More

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How to detect late-onset inborn errors of metabolism in patients with movement disorders - A modern diagnostic approach.

Parkinsonism Relat Disord 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands. Electronic address:

We propose a modern approach to assist clinicians to recognize and diagnose inborn errors of metabolism (IEMs) in adolescents and adults that present with a movement disorder. IEMs presenting in adults are still largely unexplored. These disorders receive little attention in neurological training and daily practice, and are considered complicated by many neurologists. Read More

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Difficulties in the dietary management of a girl with two diseases requiring a special diet.

J Mother Child 2021 Jan 29;22(3):225-228. Epub 2021 Jan 29.

Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland.

3-Methylcrotonylglycinuria (3-MCG) is an autosomal recessive inborn error of leucine metabolism caused by the deficiency of 3-methylocrotonyl-CoA carboxylase (3-MCC deficiency). It is the most commonly detected organic aciduria in newborn screening conducted by tandem mass spectrometry (MS/MS) [1, 2]. The clinical phenotype is heterogeneous, ranging from asymptomatic to acute metabolic decompensations [3, 4]. Read More

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January 2021

Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism.

Commun Biol 2021 Mar 19;4(1):367. Epub 2021 Mar 19.

Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7, Nijmegen, the Netherlands.

The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their pathophysiology. A primary metabolite that accumulates in the inborn error phenylketonuria is phenylalanine, however its levels do not always directly correlate with clinical outcomes. Here we combine infrared ion spectroscopy and NMR spectroscopy to identify the Phe-glucose Amadori rearrangement product as a biomarker for phenylketonuria. Read More

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A novel small molecule approach for the treatment of propionic and methylmalonic acidemias.

Mol Genet Metab 2021 Mar 10. Epub 2021 Mar 10.

HemoShear Therapeutics, Inc., Charlottesville, VA, USA.

Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) are inborn errors of metabolism affecting the catabolism of valine, isoleucine, methionine, threonine and odd-chain fatty acids. These are multi-organ disorders caused by the enzymatic deficiency of propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT), resulting in the accumulation of propionyl-coenzyme A (P-CoA) and methylmalonyl-CoA (M-CoA in MMA only). Primary metabolites of these CoA esters include 2-methylcitric acid (MCA), propionyl-carnitine (C3), and 3-hydroxypropionic acid, which are detectable in both PA and MMA, and methylmalonic acid, which is detectable in MMA patients only (Chapman et al. Read More

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Characteristics and quality of systematic reviews and meta-analyses of observational nutritional epidemiology: a cross-sectional study.

Am J Clin Nutr 2021 Mar 19. Epub 2021 Mar 19.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Background: Dietary recommendations and policies should be guided by rigorous systematic reviews. Reviews that are of poor methodological quality may be ineffective or misleading. Most of the evidence in nutrition comes from nonrandomized studies of nutritional exposures (usually referred to as nutritional epidemiology studies), but to date methodological evaluations of the quality of systematic reviews of such studies have been sparse and inconsistent. Read More

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Steroid sulfation in adrenal tumors.

J Clin Endocrinol Metab 2021 Mar 19. Epub 2021 Mar 19.

Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.

Context: The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multi-step enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers. Read More

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Homocysteine - what is it good for?

Joshua W Miller

J Intern Med 2021 Mar 19. Epub 2021 Mar 19.

Dept. of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA.

Almost 90 years ago, Vincent du Vigneaud, who would later win the 1955 Nobel prize in chemistry, published the first in vitro synthesis of the sulfur amino acid, homocysteine [1]. Over the next several decades, homocysteine would become recognized as an important intermediate in methionine, folate and one-carbon metabolism. In the 1960s, the pathologist Kilmer McCully proposed the homocysteine theory of atherosclerosis based on observations of thromboembolic disease in young children who suffered from homocystinurias, inborn errors of metabolism that cause extreme increases of homocysteine in the blood and urine [1]. Read More

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Gene delivery using AAV8 for disease stabilization in a bimodal gene therapy approach for the treatment of ADA-deficient SCID.

Mol Ther Methods Clin Dev 2021 Mar 15;20:765-778. Epub 2021 Feb 15.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Adenosine deaminase (ADA) deficiency is an inborn error of metabolism affecting multiple systems and causing severe combined immunodeficiency. We tested intravenous administration of recombinant adeno-associated virus (AAV) 2/8-ADA vector in ADA-deficient neonate and adult mice or as part of a bimodal approach comprised of rAAV treatment at birth followed by infusion of lentiviral vector (LV)-modified lineage-depleted bone marrow cells at 8 weeks. ADA mice treated with rAAV and enzyme replacement therapy (ERT) for 30 days were rescued from the lethal pulmonary insufficiency, surviving out to 180 days without further treatment. Read More

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Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency.

J Med Genet 2021 Mar 18. Epub 2021 Mar 18.

Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, Normandy Center for Genomic and Personalized Medicine, Rouen, France

Introduction: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB).

Methods: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed.

Results: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Read More

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Validation of plasma amino acid profile using UHPLC-mass spectrometer (QDa) as a screening method in a metabolic disorders reference centre: Performance and accreditation concerns.

Clin Biochem 2021 Mar 15. Epub 2021 Mar 15.

Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Tours, Tours, France; Unité INSERM U1253, équipe "neurogénomique et physiopathologie neuronale", Université de Tours, Tours, France; Centre de référence des maladies héréditaires de métabolisme - filière G2M, France.

Introduction: Amino acid (AA) analysis in plasma is essential for diagnosis and monitoring of inborn errors of metabolism (IEM). The efficacy of patient management is governed by the rapidity of AA profile availability, along with the robustness of the method. French quality guidelines and progress made in analytical techniques have led biologists to develop AA profile exploration via mass spectrometry (MS). Read More

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Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry.

Anal Chim Acta 2021 Apr 4;1154:338259. Epub 2021 Feb 4.

Swansea University Medical School, ILS1 Building, Singleton Park, Swansea, SA2 8PP, Wales, UK.

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography - tandem mass spectrometry. Read More

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Oxidative degradation and mineralization of the endocrine disrupting chemical bisphenol-A by an eco-friendly system based on UV-solar/HO with reduction of genotoxicity and cytotoxicity levels.

Sci Total Environ 2021 May 22;770:145296. Epub 2021 Jan 22.

Postgraduate Program of Chemical Engineering, State University of Maringa - UEM, Av. Colombo, 5790, Maringa, Parana CEP: 87020-900, Brazil.

A solar-driven advanced oxidation process at a lab scale was studied for the degradation and mineralization of the known endocrine disrupting chemical (EDC), bisphenol A (BPA). Preliminary tests were performed varying the irradiation source, BPA/HO ratio, temperature, initial HO concentration, initial solution pH, and initial BPA concentration, then, the operational conditions of the UV-solar/HO were optimized by a response surface methodology (RSM), providing the following responses: UV-solar/HO process at pH 3.0, [BPA] = 25 mg L, [HO] = 350 mg L, T = 50 °C, achieving BPA degradation of 77. Read More

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