DOCSLIB.ORG

Multiple Acyl-Coa Dehydrogenase Deficiency with Variable

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Multiple Acyl-Coa Dehydrogenase Deficiency with Variable G C A T T A C G G C A T genes Article Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe Orna Staretz-Chacham 1,2,* , Shirly Amar 3, Shlomo Almashanu 4, Ben Pode-Shakked 5,6, Ann Saada 7,8 , Ohad Wormser 9 and Eli Hershkovitz 2,10 1 Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Beer Sheva 84101, Israel 2 Faculty of Health Sciences, Ben-Gurion University, Beer Sheva 84101, Israel; [email protected] 3 Genetic Lab, Soroka University Medical Center, Beer Sheva 84101, Israel; [email protected] 4 National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat Gan 52621, Israel; [email protected] 5 Metabolic Disease Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 52621, Israel; [email protected] 6 Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 39040, Israel 7 Hadassah Medical Center, Department of Genetics, Jerusalem 911201, Israel; [email protected] 8 Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 911201, Israel 9 The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84101, Israel; [email protected] 10 Department of Pediatrics D, Soroka Medical Center, Beer Sheva 84101, Israel * Correspondence: [email protected]; Tel.: +972-545-713-191 Abstract: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a fatty acid and amino acid Citation: Staretz-Chacham, O.; Amar, oxidation defect caused by a deficiency of the electron-transfer flavoprotein (ETF) or the electron- S.; Almashanu, S.; Pode-Shakked, B.; transfer flavoprotein dehydrogenase (ETFDH). There are three phenotypes of the disease, two Saada, A.; Wormser, O.; Hershkovitz, neonatal forms and one late-onset. Previous studies have suggested that there is a phenotype– E. Multiple Acyl-CoA Dehydrogenase genotype correlation. We report on six patients from a single Bedouin tribe, five of whom were Deficiency with Variable Presentation sequenced and found to be homozygous to the same variant in the ETFDH gene, with variable severity Due to a Homozygous Mutation in a and age of presentation. The variant, NM_004453.3 (ETFDH): c.524G>A, p.(R175H), was previously Bedouin Tribe. Genes 2021, 12, 1140. recognized as pathogenic, although it has not been reported in the literature in a homozygous state https://doi.org/10.3390/genes12081140 before. R175H is located near the FAD binding site, likely affecting the affinity of FAD for EFT:QO. Academic Editors: Michele Cioffi and The single homozygous ETFDH pathogenic variant was found to be causing MADD in this cohort Maria Teresa Vietri with an unexpectedly variable severity of presentation. The difference in severity could partly be explained by early diagnosis via newborn screening and early treatment with the FAD precursor Received: 30 June 2021 riboflavin, highlighting the importance of early detection by newborn screening. Accepted: 23 July 2021 Published: 28 July 2021 Keywords: multiple acyl-CoA dehydrogenase deficiency (MADD); electron-transfer flavoprotein (ETF); electron-transfer flavoprotein dehydrogenase (ETFDH); genotype; phenotype Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Multiple acyl-CoA dehydrogenase deficiency (MADD) is a fatty acid and amino acid oxidation defect also known as glutaric aciduria type II. Its estimated prevalence is 1 in 750,000–2,000,000 newborns [1] with a much higher prevalence in China [2]. Copyright: © 2021 by the authors. MADD affects mitochondrial fatty acid oxidation as well as the catabolism of branched Licensee MDPI, Basel, Switzerland. amino acids, lysine and tryptophan [3]. The disease is caused by a deficiency of ei- This article is an open access article ther electron-transfer flavoprotein (ETF) or electron-transfer flavoprotein dehydrogenase distributed under the terms and (ETFDH). ETF is composed of α and β subunits, encoded by the ETFA and ETFB genes, conditions of the Creative Commons respectively, as well as electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF- Attribution (CC BY) license (https:// QO) [4,5], encoded by ETFDH [4,6]. MADD is inherited in an autosomal recessive manner. creativecommons.org/licenses/by/ 4.0/). Genes 2021, 12, 1140. https://doi.org/10.3390/genes12081140 https://www.mdpi.com/journal/genes Genes 2021, 12, x FOR PEER REVIEW 2 of 9 Genes 2021, 12, 1140 respectively, as well as electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-2 of 9 QO) [4,5], encoded by ETFDH [4,6]. MADD is inherited in an autosomal recessive manner. There are three types of the disease based on clinical symptomatology: a neonatal- onset formThere with are threecongenital types anomalies of the disease (type based I), a neonatal-onset on clinical symptomatology: form without congenital a neonatal- anomaliesonset form (type with II) congenital and a late-onset anomalies form (type (type I), III). a neonatal-onset form without congenital anomaliesThe two (type neonatal-onset II) and a late-onset forms are form usually (type fa III).tal, and affected patients develop severe non-ketoticThe two hypoglycemia neonatal-onset and forms metabolic are usually acidosis fatal, with and multisystem affected patients involvement develop accom- severe paniednon-ketotic by the hypoglycemia excretion of large and metabolicamounts of acidosis fatty acids with and multisystem branched-chain involvement amino accom- acid metabolitespanied by the[6]. excretionThose with of congenital large amounts anomalies of fatty usually acids and succumb branched-chain during the amino neonatal acid period,metabolites while [those6]. Those without with anom congenitalalies die anomalies during the usually first months succumb of during life due the to neonatal severe cardiomyopathyperiod, while those or, if without they survive anomalies longer, die tend during to develop the first episodes months of Reye life due syndrome- to severe likecardiomyopathy decompensations or, if [3]. they survive longer, tend to develop episodes of Reye syndrome-like decompensationsThe third or late-onset [3]. form has a wide spectrum of presentation, with either recur- rent episodes,The third triggered or late-onset by metabolic form has astress, wide of spectrum non-ketotic of presentation, hypoglycemia, with vomiting, either recurrent leth- argy,episodes, metabolic triggered acidosis by metabolicand hepatomegaly, stress, of non-ketoticor recurrent hypoglycemia, episodes of muscle vomiting, involvement lethargy, presentingmetabolic as acidosis weakness and and hepatomegaly, pain [3,6]. or recurrent episodes of muscle involvement pre- sentingOlsen as et weakness al., among and others, pain [3 have,6]. previously reported a clear genotype–phenotype correlationOlsen with et al., respect among to disease others, haveseverity previously [6,7]. reported a clear genotype–phenotype correlationWe present with here respect six topatients disease from severity an extended [6,7]. Bedouin tribe, of which five were found Weto be present homozygous here six patientsto the same from path an extendedogenic variant Bedouin c.524G>A, tribe, of p.(R175H) which five werein the found ET- FDHto be gene, homozygous with variable to the severity same and pathogenic age at presentation. variant c.524G>A, p.(R175H) in the ETFDH gene, with variable severity and age at presentation. 2. Materials and Methods 2. Materials and Methods Clinical and biochemical details were collected from six patients, all from the same Clinical and biochemical details were collected from six patients, all from the same extended Bedouin family (Figure 1). Five of them were found to be homozygous to the extended Bedouin family (Figure1). Five of them were found to be homozygous to the same mutation in the ETFDH gene. same mutation in the ETFDH gene. Figure 1. Pedigree of the consanguineous extended Bedouin family studied. Individuals affected Figure 1. Pedigree of the consanguineous extended Bedouin family studied. Individuals with MADD are represented by full symbols. Patient V1 succumbed before molecular investigations affected with MADD are represented by full symbols. Patient V1 succumbed before mo- were performed. lecular investigations were performed. ® TheThe automated automated extraction extraction of of DNA DNA was was performed performed using using the the QIAsymphony QIAsymphony® DSPDSP DNADNA Midi Midi Kit Kit (Qiagen, (Qiagen, Hilden, Germany)Germany) following following the the manufacturer’s manufacturer’s recommendations. recommenda- µ tions.DNA DNA was dilutedwas diluted in approximately in approximately 120 L120 ofμ bufferL of buffer ATE. DNAATE. DNA concentration concentration and quality and qualitywas quantified was quantified using ausing Nanodrop a Nanodrop ND-2000 ND spectrophotometer-2000 spectrophotometer (Nanodrop (Nanodrop Technologies, Tech- Wilmington, DE, USA). nologies, Wilmington, DE, USA). Primer3 [8] was used for designing primers FW-AAAGTGTGACCATCAATGTAGCA Primer3 [8] was used for designing primers FW-AAAGTGTGAC- REV-AAACAAAACTATACAAACCTCAGCAG for amplification of a 263 bp fragment CATCAATGTAGCA REV-AAACAAAACTATACAAACCTCAGCAG for amplification of the ETFDH gene (NM_004453.3) containing the mutation c.524G>A; p.(R175H). PCR optimal annealing temperature was determined. Cycle sequencing was performed in both directions using amplification primers
Load more

Recommended publications
  • DEPARTMENT of PUBLIC HEALTH and ENVIRONMENT 1 Laboratory
    Document 2 HRG Page 46 of 48 1 DEPARTMENT OF PUBLIC HEALTH AND ENVIRONMENT 2 Laboratory Services Division 3 NEWBORN SCREENING AND SECOND NEWBORN SCREENING 4 5 CCR 1005-4 5 Adopted by the Board of Health on _______________; effective ______________. 6 _________________________________________________________________________ 7 ***** 8 SECTION 2: NEWBORN SCREENING REQUIREMENTS FOR NAMED SUBMITTERS 9 ***** 10 2.4 List of Conditions for Newborn Screening 11 The Laboratory shall conduct screening tests for the following conditions: 12 2.4.1 Phenylketonuria 13 2.4.2 Congenital Hypothyroidism 14 2.4.3 Hemoglobinopathies 15 2.4.4 Galactosemia 16 2.4.5 Cystic Fibrosis 17 2.4.6 Biotinidase Deficiency 18 2.4.7 Congenital Adrenal Hyperplasia 19 2.4.8 Medium Chain Acyl-CoA Dehydrogenase Deficiency 20 2.4.9 Very Long Chain Acyl-CoA Dehydrogenase Deficiency 21 2.4.10 Long-Chain L-3-Hydroxy Acyl-CoA Dehydrogenase Deficiency 22 2.4.11 Trifunctional Protein Deficiency 23 2.4.12 Carnitine Acyl-Carnitine Translocase Deficiency 24 2.4.13 Short Chain Acyl-CoA Dehydrogenase Deficiency 25 2.4.14 Carnitine Palmitoyltransferase II Deficiency 26 2.4.15 Glutaric Acidemia Type 2 27 2.4.16 Arginosuccinic Acidemia 28 2.4.17 Citrullinemia Document 2 HRG Page 47 of 48 29 2.4.18 Tyrosinemia 30 2.5.19 Hypermethionemia 31 2.4.20 Maple Syrup Urine Disease 32 2.4.21 Homocystinuria 33 2.4.22 Isovaleric Acidemia 34 2.4.23 Glutaric Acidemia Type 1 35 2.5.24 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency 36 2.4.25 Multiple Carboxylase Deficiency 37 2.4.26 3-Methylcrotonyl-CoA
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Deciphering the Gene Expression Profile of Peroxisome Proliferator
    Chen et al. J Transl Med (2016) 14:157 DOI 10.1186/s12967-016-0871-3 Journal of Translational Medicine RESEARCH Open Access Deciphering the gene expression profile of peroxisome proliferator‑activated receptor signaling pathway in the left atria of patients with mitral regurgitation Mien‑Cheng Chen1*, Jen‑Ping Chang2, Yu‑Sheng Lin3, Kuo‑Li Pan3, Wan‑Chun Ho1, Wen‑Hao Liu1, Tzu‑Hao Chang4, Yao‑Kuang Huang5, Chih‑Yuan Fang1 and Chien‑Jen Chen1 Abstract Background: Differentially expressed genes in the left atria of mitral regurgitation (MR) pigs have been linked to peroxisome proliferator-activated receptor (PPAR) signaling pathway in the KEGG pathway. However, specific genes of the PPAR signaling pathway in the left atria of MR patients have never been explored. Methods: This study enrolled 15 MR patients with heart failure, 7 patients with aortic valve disease and heart failure, and 6 normal controls. We used PCR assay (84 genes) for PPAR pathway and quantitative RT-PCR to study specific genes of the PPAR pathway in the left atria. Results: Gene expression profiling analysis through PCR assay identified 23 genes to be differentially expressed in the left atria of MR patients compared to normal controls. The expressions of APOA1, ACADM, FABP3, ETFDH, ECH1, CPT1B, CPT2, SLC27A6, ACAA2, SMARCD3, SORBS1, EHHADH, SLC27A1, PPARGC1B, PPARA and CPT1A were significantly up-regulated, whereas the expression of PLTP was significantly down-regulated in the MR patients compared to normal controls. The expressions of HMGCS2, ACADM, FABP3, MLYCD, ECH1, ACAA2, EHHADH, CPT1A and PLTP were significantly up-regulated in the MR patients compared to patients with aortic valve disease.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Resveratrol Regulates Mitochondrial Reactive Oxygen Species Homeostasis Through Sirt3 Signaling Pathway in Human Vascular Endothelial Cells
    Citation: Cell Death and Disease (2014) 5, e1576; doi:10.1038/cddis.2014.530 OPEN & 2014 Macmillan Publishers Limited All rights reserved 2041-4889/14 www.nature.com/cddis Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells X Zhou1, M Chen1, X Zeng1, J Yang1, H Deng1, L Yi*,1 and M-t Mi*,1 Mitochondrial reactive oxygen species (mtROS) homeostasis plays an essential role in preventing oxidative injury in endothelial cells, an initial step in atherogenesis. Resveratrol (RSV) possesses a variety of cardioprotective activities, however, little is known regarding the effects of RSV on mtROS homeostasis in endothelial cells. Sirt3 is a mitochondrial deacetylase, which plays a key role in mitochondrial bioenergetics and is closely associated with oxidative stress. The goal of the study is to investigate whether RSV could attenuate oxidative injury in endothelial cells via mtROS homeostasis regulation through Sirt3 signaling pathway. We found that pretreatment with RSV suppressed tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in human umbilical vein endothelial cells (HUVECs) by increasing cell viability, inhibiting cell apoptosis, repressing collapse of mitochondrial membrane potential and decreasing mtROS generation. Moreover, the enzymatic activities of isocitrate dehydrogenase 2 (IDH2), glutathione peroxidase (GSH-Px) and manganese superoxide dismutase (SOD2) as well as deacetylation of SOD2 were increased by RSV pretreatment, suggesting RSV notably enhanced mtROS scavenging in t-BHP-induced endothelial cells. Meanwhile, RSV remarkably reduced mtROS generation by promoting Sirt3 enrichment within the mitochondria and subsequent upregulation of forkhead box O3A (FoxO3A)-mediated mitochondria-encoded gene expression of ATP6, CO1, Cytb, ND2 and ND5, thereby leading to increased complex I activity and ATP synthesis.
    [Show full text]
  • Annual Symposium of the Society for the Study of Inborn Errors of Metabolism Birmingham, UK, 4 – 7 September 2012
    J Inherit Metab Dis (2012) 35 (Suppl 1):S1–S182 DOI 10.1007/s10545-012-9512-z ABSTRACTS Annual Symposium of the Society for the Study of Inborn Errors of Metabolism Birmingham, UK, 4 – 7 September 2012 This supplement was not sponsored by outside commercial interests. It was funded entirely by the SSIEM. 01. Amino Acids and PKU O-002 NATURAL INHIBITORS OF CARNOSINASE (CN1) O-001 Peters V1 ,AdelmannK2 ,YardB2 , Klingbeil K1 ,SchmittCP1 , Zschocke J3 3-HYDROXYISOBUTYRIC ACID DEHYDROGENASE DEFICIENCY: 1Zentrum für Kinder- und Jugendmedizin de, Heidelberg, Germany IDENTIFICATION OF A NEW INBORN ERROR OF VALINE 2Universitätsklinik, Mannheim, Germany METABOLISM 3Humangenetik, Innsbruck, Austria Wanders RJA1 , Ruiter JPN1 , Loupatty F.1 , Ferdinandusse S.1 , Waterham HR1 , Pasquini E.1 Background: Carnosinase degrades histidine-containing dipeptides 1Div Metab Dis, Univ Child Hosp, Amsterdam, Netherlands such as carnosine and anserine which are known to have several protective functions, especially as antioxidant agents. We recently Background, Objectives: Until now only few patients with an established showed that low carnosinase activities protect from diabetic nephrop- defect in the valine degradation pathway have been identified. Known athy, probably due to higher histidine-dipeptide concentrations. We deficiencies include 3-hydroxyisobutyryl-CoA hydrolase deficiency and now characterized the carnosinase metabolism in children and identi- methylmalonic semialdehyde dehydrogenase (MMSADH) deficiency. On fied natural inhibitors of carnosinase. the other hand many patients with 3-hydroxyisobutyric aciduria have been Results: Whereas serum carnosinase activity and protein concentrations described with a presumed defect in the valine degradation pathway. To correlate in adults, children have lower carnosinase activity although pro- identify the enzymatic and molecular defect in a group of patients with 3- tein concentrations were within the same level as for adults.
    [Show full text]
  • Glutaric Acidemia Type II
    Disease Name Glutaric acidemia type 2 Alternate name(s) Glutaric aciduria II, Glutaryl-CoA dehydrogenase deficiency Acronym GA2, GA-II Disease Classification Organic Acid Disorder Variants Yes Variant name Riboflavin responsive GA1 Symptom onset Infancy (typically 2- 37 months) Symptoms Macrocephaly may be present at birth, acute encephalitic-like crises; neurodegenerative disorder with spasticity, dystonia, choreoathetosis, ataxia and dyskinesia, seizures, hypotonia, death due to Reye-like syndrome. Natural history without treatment Possible developmental delay due to encephalitis-like crisis; neurologic deterioration including spasticity, dystonic cerebral palsy. May have neurologic signs with normal IQ. Some individuals may be asymptomatic. Natural history with treatment If instituted before any damage occurs, normal outcome may occur. Risk for neurologic damage is highest in first few years. Some evidence that treatment may slow neurologic deterioration. Treatment Lysine and tryptophan restricted diet, riboflavin supplementation, carnitine supplementation. Rapid treatment of intercurrent illness with intravenous glucose, carnitine and appropriate supportive measures. Other Profuse sweating has been reported. Neuroradiographic findings of frontotemporal atrophy on CT or MRI with increased CSF containing spaces in the sylvian fissures and anterior to the temporal lobes. Also decreased attenuation in cerebral white matter on CT and increased signal intensity on MRI. Basal ganglia changes. Physical phenotype Macrocephaly, cerebral palsy
    [Show full text]
  • Metabolic Targets of Coenzyme Q10 in Mitochondria
    antioxidants Review Metabolic Targets of Coenzyme Q10 in Mitochondria Agustín Hidalgo-Gutiérrez 1,2,*, Pilar González-García 1,2, María Elena Díaz-Casado 1,2, Eliana Barriocanal-Casado 1,2, Sergio López-Herrador 1,2, Catarina M. Quinzii 3 and Luis C. López 1,2,* 1 Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, 18016 Granada, Spain; [email protected] (P.G.-G.); [email protected] (M.E.D.-C.); [email protected] (E.B.-C.); [email protected] (S.L.-H.) 2 Centro de Investigación Biomédica, Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain 3 Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA; [email protected] * Correspondence: [email protected] (A.H.-G.); [email protected] (L.C.L.); Tel.: +34-958-241-000 (ext. 20197) (L.C.L.) Abstract: Coenzyme Q10 (CoQ10) is classically viewed as an important endogenous antioxidant and key component of the mitochondrial respiratory chain. For this second function, CoQ molecules seem to be dynamically segmented in a pool attached and engulfed by the super-complexes I + III, and a free pool available for complex II or any other mitochondrial enzyme that uses CoQ as a cofactor. This CoQ-free pool is, therefore, used by enzymes that link the mitochondrial respiratory chain to other pathways, such as the pyrimidine de novo biosynthesis, fatty acid β-oxidation and amino acid catabolism, glycine metabolism, proline, glyoxylate and arginine metabolism, and sulfide oxidation Citation: Hidalgo-Gutiérrez, A.; metabolism. Some of these mitochondrial pathways are also connected to metabolic pathways González-García, P.; Díaz-Casado, in other compartments of the cell and, consequently, CoQ could indirectly modulate metabolic M.E.; Barriocanal-Casado, E.; López-Herrador, S.; Quinzii, C.M.; pathways located outside the mitochondria.
    [Show full text]
  • Genomic Evidence of Reactive Oxygen Species Elevation in Papillary Thyroid Carcinoma with Hashimoto Thyroiditis
    Endocrine Journal 2015, 62 (10), 857-877 Original Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis Jin Wook Yi1), 2), Ji Yeon Park1), Ji-Youn Sung1), 3), Sang Hyuk Kwak1), 4), Jihan Yu1), 5), Ji Hyun Chang1), 6), Jo-Heon Kim1), 7), Sang Yun Ha1), 8), Eun Kyung Paik1), 9), Woo Seung Lee1), Su-Jin Kim2), Kyu Eun Lee2)* and Ju Han Kim1)* 1) Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Korea 2) Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea 3) Department of Pathology, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea 4) Kwak Clinic, Okcheon-gun, Chungbuk, Korea 5) Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, Uijeongbu, Korea 6) Department of Radiation Oncology, Seoul St. Mary’s Hospital, Seoul, Korea 7) Department of Pathology, Chonnam National University Hospital, Kwang-Ju, Korea 8) Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 9) Department of Radiation Oncology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea Abstract. Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT.
    [Show full text]
  • Disorders Alphabetical by Disease Updated 1/2020
    Disorders Alphabetical by Disease updated 1/2020 Disorders Abbreviation Classification Recommended Uniform Screening Panel (RUSP) Classification 2,4 Dienoyl CoA Reductase Deficiency DE RED Fatty Acid Oxidation Disorder Secondary Condition 2-Methyl 3 Hydroxy Butyric Aciduria 2M3HBA Organic Acid Disorder Secondary Condition 2-Methyl Butyryl-CoA Dehydrogenase Deficiency 2MBG Organic Acid Disorder Secondary Condition (called 2-Methylbutyrylglycinuria on RUSP) 3-Hydroxy-3-Methylglutaryl CoA Lyase Deficiency HMG Organic Acid Disorder Core Condition 3-Methylcrotonyl CoA Carboxylase Deficiency 3MCC Organic Acid Disorder Core Condition 3-Methylglutaconic Aciduria 3MGA Organic Acid Disorder Secondary Condition Alpha-Thalassemia (Bart's Hb) Hemoglobin Bart's Hemoglobin Disorder Secondary Conditoin Argininemia, Arginase Deficiency ARG Amino Acid Disorder Secondary Condition Arginosuccinic Aciduria ASA Amino Acid Disorder Core Condition Benign Hyperphenylalaninemia PHE Amino Acid Disorder Secondary Condition Beta-Ketothiolase Deficiency BKT Organic Acid Disorder Core Condition Biopterin Defect in Cofactor Biosynthesis BIOPT (BS) Amino Acid Disorder Secondary Condition Biopterin Defect in Cofactor Regeneration BIOPT (Reg) Amino Acid Disorder Secondary Condition Biotinidase Deficiency BIO Metabolic Disorder of Biotin Recycling Core Condition Carbamoyltransferase Deficiency, Carbamoyl Phosphate Synthetase I Deficiency CPS Amino Acid Disorder Not on RUSP Carnitine Palmitoyl Transferase Deficiency Type 1 CPT I Fatty Acid Oxidation Disorder Secondary Condition
    [Show full text]
  • And Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid
    cells Review Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis Roxana Coras 1,2, Jessica D. Murillo-Saich 1 and Monica Guma 1,2,* 1 Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; [email protected] (R.C.); [email protected] (J.D.M.-S.) 2 Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, 08193 Bellaterra, Barcelona, Spain * Correspondence: [email protected] Received: 22 January 2020; Accepted: 18 March 2020; Published: 30 March 2020 Abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved the treatment of RA, patients often inquire about dietary interventions to improve RA symptoms, as they perceive pain and/or swelling after the consumption or avoidance of certain foods. There is evidence that some foods have pro- or anti-inflammatory effects mediated by diet-related metabolites. In addition, recent literature has shown a link between diet-related metabolites and microbiome changes, since the gut microbiome is involved in the metabolism of some dietary ingredients. But diet and the gut microbiome are not the only factors linked to circulating pro- and anti-inflammatory metabolites. Other factors including smoking, associated comorbidities, and therapeutic drugs might also modify the circulating metabolomic profile and play a role in RA pathogenesis. This article summarizes what is known about circulating pro- and anti-inflammatory metabolites in RA. It also emphasizes factors that might be involved in their circulating concentrations and diet-related metabolites with a beneficial effect in RA.
    [Show full text]
  • Glutaric Acidemia Type II
    Glutaric acidemia type II Description Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic ( metabolic acidosis). Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood sugar (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses. In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid- filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet. Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder. Frequency Glutaric acidemia type II is a very rare disorder; its precise incidence is unknown. It has been reported in several different ethnic groups. Causes Mutations in any of three genes, ETFA, ETFB, and ETFDH, can result in glutaric acidemia type II. The ETFA and ETFB genes provide instructions for producing two protein segments, or subunits, that come together to make an enzyme called electron transfer flavoprotein.
    [Show full text]