DOCSLIB.ORG

6 the Glycogen Storage Diseases and Related Disorders

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
6 the Glycogen Storage Diseases and Related Disorders 6 The Glycogen Storage Diseases and Related Disorders G. Peter A. Smit, Jan Peter Rake, Hasan O. Akman, Salvatore DiMauro 6.1 The Liver Glycogenoses – 103 6.1.1 Glycogen Storage Disease Type I (Glucose-6-Phosphatase or Translocase Deficiency) – 103 6.1.2 Glycogen Storage Disease Type III (Debranching Enzyme Deficiency) – 108 6.1.3 Glycogen Storage Disease Type IV (Branching Enzyme Deficiency) – 109 6.1.4 Glycogen Storage Disease Type VI (Glycogen Phosphorylase Deficiency) – 111 6.1.5 Glycogen Storage Disease Type IX (Phosphorylase Kinase Deficiency) – 111 6.1.6 Glycogen Storage Disease Type 0 (Glycogen Synthase Deficiency) – 112 6.2 The Muscle Glycogenoses – 112 6.2.1 Glycogen Storage Disease Type V (Myophosphorylase Deficiency) – 113 6.2.2 Glycogen Storage Disease Type VII (Phosphofructokinase Deficiency) – 113 6.2.3 Phosphoglycerate Kinase Deficiency – 114 6.2.4 Glycogen Storage Disease Type X (Phosphoglycerate Mutase Deficiency) – 114 6.2.5 Glycogen Storage Disease Type XII (Aldolase A Deficiency) – 114 6.2.6 Glycogen Storage Disease Type XIII (E-Enolase Deficiency) – 115 6.2.7 Glycogen Storage Disease Type XI (Lactate Dehydrogenase Deficiency) – 115 6.2.8 Muscle Glycogen Storage Disease Type 0 (Glycogen Synthase Deficiency) – 115 6.3 The Generalized Glycogenoses and Related Disorders – 115 6.3.1 Glycogen Storage Disease Type II (Acid Maltase Deficiency) – 115 6.3.2 Danon Disease – 116 6.3.3 Lafora Disease – 116 References – 116 102 Chapter 6 · The Glycogen Storage Diseases and Related Disorders Glycogen Metabolism Glycogen is a macromolecule composed of glucose viding glucose and glycolytic intermediates (. Fig. 6.1). units. It is found in all tissues but is most abundant in Numerous enzymes intervene in the synthesis and deg- II liver and muscle where it serves as an energy store, pro- radation of glycogen which is regulated by hormones. Fig. 6.1. Scheme of glycogen metabolism and glycolysis. PGK, II, acid maltase (D-glucosidase); III, debranching enzyme; phosphoglycerate kinase; P, phosphate; PLD, phosphorylase limit IV, branching enzyme; V, myophosphorylase; VI, liver phosphory- dextrin; UDPG, uridine diphosphate glucose. Roman numerals lase; VII, phosphofructokinase; IX, phosphorylase-b-kinase; indicate enzymes whose deficiencies cause liver (italics) and/or X, phosphoglycerate mutase; XI, lactate dehydrogenase; XII, fruc- muscle glycogenoses: 0 glycogen synthase, I, glucose-6-phos- tose-1,6-bisphosphate aldolase A; XIII, E-enolase phatase; 103 6 6.1 · The Liver Glycogenoses Glycogen, an important energy source, is found in most The liver glycogen storage disorders (GSDs) comprise tissues, but is especially abundant in liver and muscle. In GSD I, the hepatic presentations of GSD III, GSD IV, GSD VI, the liver, glycogen serves as a glucose reserve for the main- the liver forms of GSD IX, and GSD 0. GSD I, III, VI, and IX tenance of normoglycemia. In muscle, glycogen provides present similarly with hypoglycemia, marked hepato- energy for muscle contraction. megaly, and growth retardation. GSD I is the most Despite some overlap, the GSDs can be divided in three severe affecting both glycogen breakdown and gluco- main groups: those affecting liver, those affecting muscle, neogenesis. In GSD Ib there is additionally a disorder of and those which are generalized (. Table 6.1). GSDs are neutrophil function. Most patients with GSD III have a d enoted by a Roman numeral that reflects the historical syndrome that inc ludes hepatopathy, myopathy, and sequence of their discovery, by the deficient enzyme, or by often cardiomyo pathy. GSD VI and GSD IX are the least the name of the author of the first description. The Fanconi- severe: there is only a mild tendency to fasting hypo- Bickel syndrome is discussed in Chap. 11. glycemia, liver size normalises with age, and patients reach normal adult height. GSD IV manifests in most patients in infancy or childhood as hepatic failure with 6.1 The Liver Glycogenoses cirrhosis leading to end-stage liver disease. GSD 0 presents in infancy or early childhood with fasting The liver GSDs comprise GSD I, the hepatic presentations hypoglycemia and ketosis and, in contrast, with post- of GSD III, GSD IV, GSD VI, the liver forms of GSD IX, and prandial hyperglycemia and hyperlactatemia. Treat- GSD 0. GSD I, III, VI, and IX present with similar symp- ment is primarily dietary and aims to prevent hypoglyc- toms during infancy, with hypoglycemia, marked hepatome- emia and suppress secondary metabolic decompensa- galy, and retarded growth. GSD I is the most severe of these tion. This usually requires frequent feeds by day, and in four conditions because not only is glycogen breakdown GSD I and in some patients with GSD III, continuous impaired, but also gluconeogenesis. Most patients with nocturnal gastric feeding. GSD III have a syndrome that includes hepatopathy, myo- The muscle glycogenoses fall into two clinical pathy, and often cardiomyopathy. GSD IV manifests in groups. The first comprises GSD V, GSD VII, the muscle most patients in infancy or childhood as hepatic failure with forms of GSD IX (VIII according to McKusick), phospho- cirrhosis leading to end-stage liver disease. GSD VI and glycerate kinase deficiency (IX according to McKusick), the hepatic forms of GSD IX are the mildest forms: there is GSD X, GSD XI, GSD XII and GSD XIII, and is character- only a mild tendency to fasting hypoglycemia, liver size ised by exercise intolerance with exercise-induced normalises with age, and patients reach normal adult height. myalgia and cramps, which are often followed by rhab- GSD 0 presents in infancy or early childhood with fasting domyolysis and myoglobinuria; all symptoms are hypoglycemia and ketosis contrasting with postprandial reversible with rest. Disorders in the second group, hyperglycemia and hyperlactatemia. The muscle forms of consisting of the myopathic form of GSD III, and rare GSD III and IX are also discussed in this section. neuromuscular forms of GSD IV, manifest as sub-acute or chronic myopathies, with weakness of trunk, limb, and respiratory muscles. Involvement of other organs 6.1.1 Glycogen Storage Disease Type I (erythrocytes, central or peripheral nervous system, (Glucose-6-Phosphatase of Translo- heart, liver) is possible, as most of these enzymes de- case Deficiency) fects are not confined to skeletal muscle. Generalized glycogenoses comprise GSD II, caused GSD I, first described by von Gierke, comprises GSD Ia by the deficiency of a lysosomal enzyme, and Danon caused by deficiency of the catalytic subunit of glucose-6- disease due to the deficiency of a lysosomal membrane phosphatase (G6Pase), and GSD Ib, due to deficiency of the protein. Recent work on myoclonus epilepsy with endoplasmic reticulum (ER) glucose-6-phosphate (G6P) Lafora bodies ( Lafora disease) suggests that this is translocase. There is controversy about the existence of ER a glycogenosis, probab ly due to abnormal glycogen phosphate translocase deficiency (GSD Ic) and ER glucose synthesis. GSD II can be treated by enzyme replace- transporter deficiency (GSD Id) as distinct entities. In this ment therapy, but there is no specific treatment for chapter, the term GSD Ib includes all GSD I non-a forms. Danon and Lafora disease. Clinical Presentation A protruded abdomen, truncal obesity, rounded doll face, The glycogen storage diseases (GSDs) and related disorders hypotrophic muscles, and growth delay are conspicuous are caused by defects of glycogen degradation, glycolysis clinical findings. Profound hypoglycemia and lactic acidosis and, paradoxically, glycogen synthesis. They are all called occur readily and can be elicited by trivial events, such as glycogenoses, although not all affect glycogen breakdown. delayed meals or reduced food intake associated with inter- 104 Chapter 6 · The Glycogen Storage Diseases and Related Disorders . Table 6.1. Main features of glycogen storage diseases and related disorders Type or Defective enzyme or transporter Main tissue involved Main clinical symptoms II synonym Liver Ia Glucose-6-phosphatase Liver, kidney Hepatomegaly, short stature, hypoglycemia, lactatemia, Von hyperlipidemia Gierke Ib (non-a) Glucose-6-phosphate translocase Liver, kidney, leucocytes Same as Ia, neutropenia, infections III Debranching enzyme and sub- Liver, muscle Hepatomegaly, (cardio)myopathy, short stature, hypo- Cori, types glycemia Forbes IV Branching enzyme Liver Hepato(spleno)megaly, liver cirrhosis, rare neuromuscu- Andersen lar forms VI Liver phosphorylase Liver Hepatomegaly, short stature, Hers hypoglycemia IX Phosphorylase kinase Liver and/or muscle Hepatomegaly, short stature (myopathy), and subtypes hypoglycemia 0Glycogen synthase Liver Hypoglycemia Muscle V Myophosphorylase MuscleMyalgia, exercise intolerance, weakness Mc Ardle VII Phosphofructokinase Muscle, erythrocytes Myopathy, hemolytic anemia, Tarui and variants multisystem involvement (seizures, cardiopathy) – Phosphoglycerate kinase Muscle, erythrocytes, Exercise intolerance, hemolytic anemia central nervous system convulsions X Phosphoglycerate mutase Muscle Exercise intolerance, cramps XI Lactate dehydrogenase Muscle Exercise intolerance, cramps, skin lesions XII Aldolase A Muscle Exercise intolerance, cramps XIII E-Enolase Muscle Exercise intolerance, cramps Generalized II Lysosomal Generalized Hypotonia, cardio-myopathy Pompe D-glucosidase in lysosomes Infantile, juvenile, adult forms IIb Lysosomal-associated Heart, muscle Cardio-myopathy Pseudo membrane protein 2 Pompe Danon Lafora Enzyme defect not known Polyglucosan
Load more

Recommended publications
  • Targeted Genes and Methodology Details for Neuromuscular Genetic Panels
    Targeted Genes and Methodology Details for Neuromuscular Genetic Panels Reference transcripts based on build GRCh37 (hg19) interrogated by Neuromuscular Genetic Panels Next-generation sequencing (NGS) and/or Sanger sequencing is performed Motor Neuron Disease Panel to test for the presence of a mutation in these genes. Gene GenBank Accession Number Regions of homology, high GC-rich content, and repetitive sequences may ALS2 NM_020919 not provide accurate sequence. Therefore, all reported alterations detected ANG NM_001145 by NGS are confirmed by an independent reference method based on laboratory developed criteria. However, this does not rule out the possibility CHMP2B NM_014043 of a false-negative result in these regions. ERBB4 NM_005235 Sanger sequencing is used to confirm alterations detected by NGS when FIG4 NM_014845 appropriate.(Unpublished Mayo method) FUS NM_004960 HNRNPA1 NM_031157 OPTN NM_021980 PFN1 NM_005022 SETX NM_015046 SIGMAR1 NM_005866 SOD1 NM_000454 SQSTM1 NM_003900 TARDBP NM_007375 UBQLN2 NM_013444 VAPB NM_004738 VCP NM_007126 ©2018 Mayo Foundation for Medical Education and Research Page 1 of 14 MC4091-83rev1018 Muscular Dystrophy Panel Muscular Dystrophy Panel Gene GenBank Accession Number Gene GenBank Accession Number ACTA1 NM_001100 LMNA NM_170707 ANO5 NM_213599 LPIN1 NM_145693 B3GALNT2 NM_152490 MATR3 NM_199189 B4GAT1 NM_006876 MYH2 NM_017534 BAG3 NM_004281 MYH7 NM_000257 BIN1 NM_139343 MYOT NM_006790 BVES NM_007073 NEB NM_004543 CAPN3 NM_000070 PLEC NM_000445 CAV3 NM_033337 POMGNT1 NM_017739 CAVIN1 NM_012232 POMGNT2
    [Show full text]
  • Blueprint Genetics ENO3 Single Gene Test
    ENO3 single gene test Test code: S00654 Phenotype information Glycogen storage disease Panels that include the ENO3 gene Glycogen Storage Disorder Panel Comprehensive Metabolism Panel Hypoglycemia, Hyperinsulinism and Ketone Metabolism Panel Metabolic Myopathy and Rhabdomyolysis Panel Test Strengths The strengths of this test include: CAP accredited laboratory CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance Careful construction of clinically effective and scientifically justified gene panels Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level Our publicly available analytic validation demonstrating complete details of test performance ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this test’) Our rigorous variant classification scheme Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data Our comprehensive clinical statements Test Limitations This test does not detect the following: Complex inversions Gene conversions Balanced translocations Mitochondrial DNA variants Repeat expansion disorders unless specifically mentioned Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above non-coding variants covered by the test). This test may not reliably detect the following: Low level mosaicism (variant with a minor allele fraction of 14.6% is detected with 90% probability) Stretches of mononucleotide repeats Indels larger than 50bp Single exon deletions or duplications Variants within pseudogene regions/duplicated segments The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.
    [Show full text]
  • HEMOLYTIC ANEMIA in DISORDERS of REO CELL METABOLISM TOPICS in HEMATOLOGY Series Editor: Maxwell M
    HEMOLYTIC ANEMIA IN DISORDERS OF REO CELL METABOLISM TOPICS IN HEMATOLOGY Series Editor: Maxwell M. Wintrobe, M.D. University of Utah, Salt Lake City THE RESPIRATORY FUNCTIONS OF BLOOD Lars Garby, M.D. and Jerry Meldon, M.D. HEMOLYTIC ANEMIA IN DISORDERS OF RED CELL METABOLISM Ernest Beutler, MD. TRACE ELEMENTS AND IRON IN HUMAN METABOLISM Ananda S. Prasad, M.D. HEMOLYTIC ANEMIA IN DISORDERS OF REO CELL METABOLISM Ernest Beutler, M. O. City of Hope National Medical Center Duarte, California PLENUM MEDICAL BOOK COMPANY· New York and London Library of Congress Cataloging in Publication Data Beutler, Ernest. Hemolytic anemia in disorders of red cell metabolism. (Topics in hematology) Includes index. 1. Hemolytic anemia. 2. Erythrocyte disorders. I. Title. II. Series. CR641.7.H4B48 616.1'52 78-2391 ISBN 978-1-4684-2459-1 ISBN 978-1-4684-2457-7 (eBook) DOI 10.1007/978-1-4684-2457-7 © 1978 Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition 1978 227 West 17th Street, New York, N.Y. 10011 Plenum Medical Book Company is an imprint of Plenum Publishing Corporation All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher FOREWORD I am prepared to predict that this monograph by Dr. Ernest Beutler will long serve as a model for monographs dealing with topics in medical science. I make this bold statement because we encounter in this work a degree of accuracy and authoritativeness well beyond that found in much of the medical literature.
    [Show full text]
  • Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’
    Journal of Neuromuscular Diseases 8 (2021) 401–417 401 DOI 10.3233/JND-200621 IOS Press Systematic Review Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’ A. Mantaa,b, S. Spendiffb, H. Lochmuller¨ b,c,d,e,f and R. Thompsonb,∗ aFaculty of Medicine, University of Ottawa, Ottawa, ON, Canada bChildren’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada cDepartment of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany dCentro Nacional de An´alisis Gen´omico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain eDivision of Neurology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Canada f Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada Abstract. Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intoler- ance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and ␤-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforemen- tioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism.
    [Show full text]
  • Defective Galactose Oxidation in a Patient with Glycogen Storage Disease and Fanconi Syndrome
    Pediatr. Res. 17: 157-161 (1983) Defective Galactose Oxidation in a Patient with Glycogen Storage Disease and Fanconi Syndrome M. BRIVET,"" N. MOATTI, A. CORRIAT, A. LEMONNIER, AND M. ODIEVRE Laboratoire Central de Biochimie du Centre Hospitalier de Bichre, 94270 Kremlin-Bicetre, France [M. B., A. C.]; Faculte des Sciences Pharmaceutiques et Biologiques de I'Universite Paris-Sud, 92290 Chatenay-Malabry, France [N. M., A. L.]; and Faculte de Midecine de I'Universiti Paris-Sud et Unite de Recherches d'Hepatologie Infantile, INSERM U 56, 94270 Kremlin-Bicetre. France [M. 0.1 Summary The patient's diet was supplemented with 25-OH-cholecalci- ferol, phosphorus, calcium, and bicarbonate. With this treatment, Carbohydrate metabolism was studied in a child with atypical the serum phosphate concentration increased, but remained be- glycogen storage disease and Fanconi syndrome. Massive gluco- tween 0.8 and 1.0 mmole/liter, whereas the plasma carbon dioxide suria, partial resistance to glucagon and abnormal responses to level returned to normal (18-22 mmole/liter). Rickets was only carbohydrate loads, mainly in the form of major impairment of partially controlled. galactose utilization were found, as reported in previous cases. Increased blood lactate to pyruvate ratios, observed in a few cases of idiopathic Fanconi syndrome, were not present. [l-14ClGalac- METHODS tose oxidation was normal in erythrocytes, but reduced in fresh All studies of the patient and of the subjects who served as minced liver tissue, despite normal activities of hepatic galactoki- controls were undertaken after obtaining parental or personal nase, uridyltransferase, and UDP-glucose 4epirnerase in hornog- consent. enates of frozen liver.
    [Show full text]
  • Improvement of the Nutritional Management of Glycogen Storage Disease Type I
    1 Improvement of the nutritional management of glycogen storage disease type I Kaustuv Bhattacharya Presented for the degree of MD (res) at University College London 2 “The roots below the earth claim no rewards for making the branches fruitful” Sir Rabrindranath Tagore Stray Birds (1917) Acknowledgements Whilst this thesis is my own work, it is the product of several helpful discussions with many people around the world. It was conducted under the supervision of Philip Lee who, since completion of the data collection, faced bigger personal challenges than he could have imagined. I hope that this work is a fitting conclusion to one strategic direction, of some of his research, which I hope he can be proud of. I am very grateful for his help. Peter Clayton has been a source of inspiration throughout my “metabolic” career and his guidance throughout this process has been very gratefully received. I appreciate the tolerance of my other colleagues at Queen Square and Great Ormond Street Hospital that have accommodated in different ways. The dietetic experience of Maggie Lilburn has been invaluable to this work. Simon Eaton has helped tremendously with performing the assays in chapter 5. I would also like to thank, David Morley, Amy Cole, Martin Christian, and Bridget Wilcken for their constructive thoughts. None of this work would have been possible without the Murphy family’s generous support. I thank the Dromintee Trust for keeping me in worthwhile employment. I would like to thank the patients who volunteered and gave me so much of their time. The Association for Glycogen Storage Disease (UK), Glycologic Ltd and Vitaflo Ltd have also sponsored these trials and hopefully facilitated a better experience for patients.
    [Show full text]
  • Datasheet: VPA00226
    Datasheet: VPA00226 Description: RABBIT ANTI ALDOA Specificity: ALDOA Format: Purified Product Type: PrecisionAb™ Polyclonal Isotype: Polyclonal IgG Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse, Rat Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Rabbit Ig fraction prepared by ammonium sulphate precipitation Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN3) Stabilisers Immunogen KLH conjugated synthetic peptide between 66-95 amino acids from the N-terminal region of human ALDOA External Database UniProt: Links P04075 Related reagents Entrez Gene: 226 ALDOA Related reagents Page 1 of 2 Synonyms ALDA Specificity Rabbit anti Human ALDOA antibody recognizes fructose-bisphosphate aldolase A, also known as epididymis secretory sperm binding protein Li 87p, fructose-1,6-bisphosphate triosephosphate-lyase, lung cancer antigen NY-LU-1 and muscle-type aldolase. Encoded by the ALDOA gene, fructose-bisphosphate aldolase A is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
    [Show full text]
  • General Nutrition Guidelines for Glycogen Storage Disease Type III
    General Nutrition Guidelines For Glycogen Storage Disease Type III Glycogen Storage Disease Type III (GSDIII) is a genetic metabolic disorder which causes the inability to break down glycogen to glucose. Glycogen is a stored form of sugar in the body. Glucose (sugar) is the main source of fuel for the body and brain. GSD IIIa causes the inability of the liver and muscles to breakdown glycogen to glucose. GSD IIIb causes the inability of the liver to breakdown glycogen to glucose. As a result of the inability to breakdown glycogen, patients with GSDIII are at risk for low blood sugars (hypoglycemia) during periods of fasting. Patients with GSDIIIa also do not have the ability to access glycogen in their muscles as well. The lack of glycogen access in the muscles causes muscle damage as the muscle do not have a fuel to aid them in working. The following is a recommended general nutrition guideline for those with GSDIII to help maximize blood sugar control, nutrition, energy, and hopefully minimize muscle damage for those with GSDIIIa. Protein What is protein? Protein is a macronutrient (like carbohydrate and fat) and is required for proper growth and development. In GSDIII, the most important role that protein serves is a way for the body to make glucose since those with GSDIII do not have access to stored sugars (glycogen). Protein also serves as the building blocks for our cells, is also necessary to make antibodies which help our bodies fight off illnesses, make up hormones, enzymes, and even our DNA. With GSD type III, it is very important to make sure you are getting all the protein that your body needs.
    [Show full text]
  • Pathogenic Variant Identified
    PERFORMED AT PHOSPHORUS DIAGNOSTICS, 400 PLAZA DRIVE, SUITE 401, SECAUCUS, NJ 07094 ORDERING PRACTICE JANE DOE TEST INFORMATION Practice Code: 100 DOB: 1973-02-19 Panel: Pan Arrhythmia and Cardiomyopathy Panel Sample Cardiology Clinic Gender: Female Indication: Diagnostic for Patient History 374 Broadway Ethnicity: European New York, NY 10001 Procedure ID: 87000 Physician: Dr. Sample Kit Barcode: 201612092248585 Specimen: Blood, #10000 Specimen Collected: 2016-01-12 Specimen Received: 2016-01-13 Specimen Analyzed: 2016-01-21 Report Generated: 2016-02-03 SUMMARY OF RESULTS Positive: Pathogenic Variant Identified GENE LOCATION VARIANT INHERITANCE ZYGOSITY CLASSIFICATION KCNQ1 Exon 6; Chrom 11 c.914G>A Autosomal Dominant Heterozygous PATHOGENIC (p.Trp205Ter) MYH7 Exon 38; Chrom 14 c.26647G>A Unknown Heterozygous UNCERTAIN (p.Glu1883Lys) SIGNIFICANCE INTERPRETATION This patient is heterozygous for the c.914G>A (p.Trp205Ter) pathogenic variant in KCNQ1. This result indicates that this patient may be affected with, or predisposed to developing, long QT syndrome. This patient is also heterozygous for the c.185G>A (p.Lys65Ala) variant of unknown clinical significance in MYH7. The contribution of this variant to the patient’s phenotype is unknown. RECOMMENDATIONS Clinical follow-up with a cardiologist or cardiogeneticist is recommended to discuss medical management. Genetic counseling is recommended for this patient. Genetic testing may be useful in identifying family members at risk for disease. Genetic counseling is recommended for all individuals undergoing genetic testing. VARIANT INFORMATION PATHOGENIC KCNQ1 c.914G>A (p.Trp305Ter) This variant leads to a premature termination at codon 305, which is expected to result in an absent or significantly disrupted protein product.
    [Show full text]
  • Maladies Convention Mal
    maladies métaboliques monogéniques héréditaires rares 1 avenant à la convention avec les centres de référence – annexe OMIM # FULL NAME A. disorders of amino acid metabolism 1 261600 classical phenylketonuria and hyperphenylala- ninemia 2 261640 phenylketonuria due to PTPS deficiency 3 261630 phenylketonuria due to DHPR deficiency 4 264070 phenylketonuria due to PCD deficiency 5 128230 DOPA-responsive dystonia (TH, SPR, GCH1) 6 248600 leucinose, maple syrup urine disease (MSUD) 7 276700 tyrosinemia type 1 8 276600 tyrosinemia type 2 9 276710 tyrosinemia type 3 10 203500 alkaptonuria 11 236200 homocystinuria, B6 responsive and non responsive 12 236250 homocystinuria due to MTHFR deficiency 13 236270-250940 homocystinuria-megaloblastic anemia Cbl E & G type 14 250850 methionine S-adenosyltransferase deficiency 15 606664 glycine N-methyltransferase deficiency 16 180960 S-adenosylhomocystine hydrolase deficiency 17 237300 hyperammonemia due to CPS deficiency 18 311250 hyperammonemia due to OTC deficiency 19 215700 citrullinemia type I 20 605814-603471 citrullinemia type II 21 207900 argininosuccinic aciduria (ASL deficiency) 22 207800 argininemia (arginase deficiency) 23 237310 hyperammonemia due to NAGS deficiency 24 238970 hyperornithinemia, hyperammonemia, homocitrulli- nuria (HHH) 25 222700 lysinuric protein intolerance 26 258870 gyrate atrophy, B6 responsive or non responsive 27 238700 hyperlysinemia (alpha-aminoadipic semialdehyde synthase deficiency) 28 238300-330-310 non ketotic hyperglycinaemia 29 234500 hartnup disorder 30 601815-172480
    [Show full text]
  • Progress in the Biological Function of Alpha-Enolase
    Animal Nutrition 2 (2016) 12e17 Contents lists available at ScienceDirect Animal Nutrition journal homepage: http://www.keaipublishing.com/en/journals/aninu/ Review article Progress in the biological function of alpha-enolase * Hong Ji 1, Jianfa Wang 1, Jingru Guo, Yue Li, Shuai Lian, Wenjin Guo, Huanmin Yang , Fanzhi Kong, Li Zhen, Li Guo, Yanzhi Liu College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China article info abstract Article history: Alpha-enolase (ENO1), also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that cata- Received 16 December 2015 lyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. It Accepted 3 February 2016 is a multifunctional glycolytic enzyme involved in cellular stress, bacterial and fungal infections, auto- Available online 2 March 2016 antigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, devel- opment and reproduction of organisms. This article mainly reviews the basic characteristics and Keywords: biological functions of ENO1. a-enolase © 2016, Chinese Association of Animal Science and Veterinary Medicine. Production and hosting Glycolysis Plasma plasminogen by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the Cancer CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Parasite 1. Introduction present article mainly reviews the basic characteristics and bio- logical functions
    [Show full text]
  • Centometabolic® COMBINING GENETIC and BIOCHEMICAL TESTING for the FAST and COMPREHENSIVE DIAGNOSTIC of METABOLIC DISORDERS
    CentoMetabolic® COMBINING GENETIC AND BIOCHEMICAL TESTING FOR THE FAST AND COMPREHENSIVE DIAGNOSTIC OF METABOLIC DISORDERS GENE ASSOCIATED DISEASE(S) ABCA1 HDL deficiency, familial, 1; Tangier disease ABCB4 Cholestasis, progressive familial intrahepatic 3 ABCC2 Dubin-Johnson syndrome ABCD1 Adrenoleukodystrophy; Adrenomyeloneuropathy, adult ABCD4 Methylmalonic aciduria and homocystinuria, cblJ type ABCG5 Sitosterolemia 2 ABCG8 Sitosterolemia 1 ACAT1 Alpha-methylacetoacetic aciduria ADA Adenosine deaminase deficiency AGA Aspartylglucosaminuria AGL Glycogen storage disease IIIa; Glycogen storage disease IIIb AGPS Rhizomelic chondrodysplasia punctata, type 3 AGXT Hyperoxaluria, primary, type 1 ALAD Porphyria, acute hepatic ALAS2 Anemia, sideroblastic, 1; Protoporphyria, erythropoietic, X-linked ALDH4A1 Hyperprolinemia, type II ALDOA Glycogen storage disease XII ALDOB Fructose intolerance, hereditary ALG3 Congenital disorder of glycosylation, type Id ALPL Hypophosphatasia, adult; Hypophosphatasia, childhood; Hypophosphatasia, infantile; Odontohypophosphatasia ANTXR2 Hyaline fibromatosis syndrome APOA2 Hypercholesterolemia, familial, modifier of APOA5 Hyperchylomicronemia, late-onset APOB Hypercholesterolemia, familial, 2 APOC2 Hyperlipoproteinemia, type Ib APOE Sea-blue histiocyte disease; Hyperlipoproteinemia, type III ARG1 Argininemia ARSA Metachromatic leukodystrophy ARSB Mucopolysaccharidosis type VI (Maroteaux-Lamy) 1 GENE ASSOCIATED DISEASE(S) ASAH1 Farber lipogranulomatosis; Spinal muscular atrophy with progressive myoclonic epilepsy
    [Show full text]