Current Research Topics in Propionic Acidemia
2011 PA Consensus Conference

Children’s National Medical Center, Washington, D.C.Reprinted from MOLECULAR GENETICS AND METABOLISM, Vol 105, No 1, 2012 Copyright (2011) with permission from Elsevier

Propionic acidemia concensus conference summary”,  Kimberly A. Chapman, Marshall L. Summar,  pp 3-4, Copyright (2011) with permission from Elsevier

Natural history of propionic acidemia” Loren Pena, Jill Franks, Kimberly A. Chapman, Andrea Gropman, Nicholas Ah Mew, Anupam Chakrapani, Eddie Island, Erin MacLeod, Dietrich Matern, Brittany Smith, Kathy Stagni, V. Reid Sutton, Keiko Ueda, Tiina Urv, Charles Venditti, Gregory M. Enns, Marshall L. Summar,

Neurologic considerations in propionic acidemia” John Schreiber, Kimberly A. Chapman, Marshall L. Summar, Nicholas Ah Mew, V. Reid Sutton, Erin MacLeod, Kathy Stagni, Keiko Ueda, Jill Franks, Eddie Island, Dietrich Matern, Loren Peña, Brittany Smith, Tiina Urv, Charles Venditti, Anupam Chakarapani, Andrea L. Gropman

Acute management of propionic acidemia”  Kimberly A. Chapman a, Andrea Gropman, Erin MacLeod, Kathy Stagni, Marshall L. Summar, Keiko Ueda, Nicholas Ah Mew, Jill Franks, Eddie Island, Dietrich Matern, Loren Pena, Brittany Smith, V. Reid Sutton, Tiina Urv, Charles Venditti, Anupam Chakrapani

Chronic Management and Health Supervision of Individuals with Propionic Acidemia” V. Reid Sutton a, Kimberly A. Chapman, Andrea L. Gropman, Erin MacLeod, Kathy Stagni, Marshall L. Summar, Keiko Ueda, Nicholas Ah Mew, Jill Franks, Eddie Island, Dietrich Matern, Loren Peña, Brittany Smith, Tina Urv, Charles Venditti, Anupam Chakarapani

2013 PAF Education Conference Presentations

2010 PAF Education Conference Videos

Organic Acidemias by Barbara Burton, MD

Survey Results by Loren Pena, MD, PhD

Nutritional Aspects of Treatment by Maryam Naziri RD, LDN

Genetics of Organic Acidemias by Katherine Kim MS

Anesthesia

Propionic Acidemia in a Four-Month-Old Male: A Case sStudy and Anesthetic Implications; H. Eugene Harker, MD, PhD, John D. Emhardt, MD, and Bryan E. Hainline, MD PhD  Anesthesia & Analgesia 2000; 91:309-311.

Intractable metabolic acidosis in a child with propionic acidemia undergoing liver transplantation -a case report
Jiyoung Ryu, Young Hee Shin, Justin Sangwook Ko, Mi Sook Gwak and Gaab-Soo Kim
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Cardiology

Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia. Baumgartner D, Scholl-Bürgi S, Sass JO, Sperl W, Schweigmann U, Stein JI, Karall D.
J Pediatr. 2007 Feb;150(2):192-7, 197.e1.

Jameson E, Walter J.

Cardiac Arrest Secondary to Long QT(C )in a Child with Propionic Acidemia.
Pediatr Cardiol. 2007 Dec 5;

Kakavand B, Schroeder VA, Di Sessa TG.

Coincidence of long QT syndrome and propionic acidemia.
Pediatr Cardiol. 2006 Jan-Feb;27(1):160-1.

Mardach R, Verity MA, Cederbaum SD.

Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy.
Mol Genet Metab. 2005 Aug;85(4):286-90.

Dermatology

Lane TN, Spraker MK, Parker SS.

Propionic acidemia manifesting with low isoleucine generalized exfoliative dermatosis.
Pediatr Dermatol. 2007 Sep-Oct;24(5):508-10.

Dietary Modifications

Yannicelli S, Acosta PB, Velazquez A, Bock HG, Marriage B, Kurczynski TW, Miller M, Korson M, Steiner RD, Rutledge L, Bernstein L, Chinsky J, Galvin-Parton P, Arnold GL.

Improved growth and nutrition status in children with methylmalonic or propionic acidemia fed an elemental medical food.
Mol Genet Metab. 2003 Sep-Oct;80(1-2):181-8.

Gene Expression

Chapman KA1, Bush WS2, Zhang Z3.

Gene expression in cell lines from propionic acidemia patients, carrier parents, and controls.

Mol Genet Metab. 2015 Aug;115(4):174-9. doi: 10.1016/j.ymgme.2015.05.004. Epub 2015 May 8.

Hearing

Brosch S, Rauffeisen A, Baur M, Michels L, Trefz FK, Pfister M.

[Propionic acidemia and sensorineural hearing loss: is there a connection at the molecular genetics level?]

HNO, 2008 Jan;56(1):37-42.

Hyperammonemia

Nicholas Ah Mew, Robert McCarter, Yevgeny Daikhin, Itzhak Nissim, Marc Yudkoff, and Mendel Tuchman
N-carbamylglutamate Augments Ureagenesis and Reduces Ammonia and Glutamine in Propionic Acidemia
Pediatrics, Jul 2010; 126: e208 – e214.

Filipowicz HR, Ernst SL, Ashurst CL, Pasquali M, Longo N.

Metabolic changes associated with hyperammonemia in patients with propionic acidemia.
Mol Genet Metab. 2006 Jun;88(2):123-30.

Tuchman M, Caldovic L. Daikhin Y, Horyn O, Nissim I, Korson M, Burton B, Yudkoff M.

N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers.

Pediatr Res. 2008 Apr 9.

Intestinal Motility

Prasad C, Nurko S, Borovoy J, Korson MS.

The importance of gut motility in the metabolic control of propionic acidemia.

J Pediatr. 2004 Apr;144(4):532-5.

Liver Transplantation

Rela M, Battula N, Madanur M, Mieli-Vergani G, Dhawan A, Champion M, Raiman J, Heaton N.

Auxiliary liver transplantation for propionic acidemia: a 10-year follow-up.
Am J Transplant. 2007 Sep;7(9):2200-3.

Barshes NR, Vanatta JM, Patel AJ, Carter BA, O’Mahony CA, Karpen SJ, Goss JA.

Evaluation and management of patients with propionic acidemia undergoing liver transplantation: a comprehensive review.
Pediatr Transplant. 2006 Nov;10(7):773-81.

Meyburg J, Hoffmann GF.

Liver transplantation for inborn errors of metabolism.
Transplantation. 2005 Sep 27;80(1 Suppl):S135-7. Review.

Kayler LK, Merion RM, Lee S, Sung RS, Punch JD, Rudich SM, Turcotte JG, Campbell DA Jr, Holmes R, Magee JC.

Long-term survival after liver transplantation in children with metabolic disorders.
Pediatr Transplant. 2002 Aug;6(4):295-300.

Metabolomics

Wikoff WR, Gangoiti JA, Barshop BA, Siuzdak G.

Metabolomics identifies perturbations in human disorders of propionate metabolism.
Clin Chem. 2007 Dec;53(12):2169-76. Epub 2007 Oct 19.

Mitochondrial Dysfunction

Schwab MA, Sauer SW, Okun JG, Nijtmans LG, Rodenburg RJ, van den Heuvel LP, Dröse S, Brandt U, Hoffmann GF, Ter Laak H, Kölker S, Smeitink JA.

Secondary mitochondrial dysfunction in propionic aciduria: a pathogenic role for endogenous mitochondrial toxins.

Biochem J. 2006 Aug 15;398(1):107-12.

Mouse Model of PA / Gene Therapy

Generation of a Hypomorphic Model of Propionic Acidemia Amenable to Gene Therapy Testing.  Guenzel AJ, Hofherr SE, Hillestad M, Barry M, Weaver E, Venezia S, Kraus JP, Matern D, Barry MA. Mol Ther. 2013 May 7. doi: 10.1038/mt.2013.68. [Epub ahead of print]

Adeno-associated virus serotype 8 (AAV8) Gene Transfer Rescues a Neonatal Lethal Murine Model of Propionic Acidemia

Randy Joseph Chandler, Suma Chandrasekaran, Nuria Carrillo-Carrasco, Julien Simon Senac, Sean Hofherr, Michael A Barry, Charles Paul Venditti.

Short-term Rescue of Neonatal Lethality in a Mouse Model of Propionic Acidemia by Gene Therapy. Hofherr S, Senac JS, Chen CY, Palmer D, Ng P, Barry MA. Hum Gene Ther. 2008 Nov 24. [Epub ahead of print] PMID: 19025475

Miyazaki T, Ohura T, Kobayashi M, Shigematsu Y, Yamaguchi S, Suzuki Y, Hata I, Aoki Y, Yang X, Minjares C, Haruta I, Uto H, Ito Y, Müller U.

Fatal propionic acidemia in mice lacking propionyl-CoA carboxylase and its rescueby postnatal, liver-specific supplementation via a transgene

J Biol Chem. 2001 Sep 21;276(38):35995-9. Epub 2001 Jul 18.

Neurology

Nguyen NH, Morland C, Gonzalez SV, Rise F, Storm-Mathisen J, Gundersen V, Hassel B.

Propionate increases neuronal histone acetylation, but is metabolized oxidatively by glia. Relevance for propionic acidemia.
J Neurochem. 2007 May;101(3):806-14.

Newborn Screening

Ophthalmology

Propionic acidemia and optic neuropathy: a report of two cases.

Arias C, Raimann E, Peredo P, Cabello JF, Castro G, Valiente A, de la Parra A, Bravo P, Okuma C, Cornejo V. JIMD Rep. 2014;12:1-4. doi: 10.1007/8904_2013_234. Epub 2013 Jul 2.

Optic nerve atrophy in propionic acidemia.

Ianchulev T, Kolin T, Moseley K, Sadun A.  Ophthalmology. 2003 Sep;110(9):1850-4.

PCC Enzyme and Mutations

Clinical characteristics and mutation analysis of propionic acidemia in Thailand.  

Vatanavicharn N, Liammongkolkul S, Sakamoto O, Kamolsilp M, Sathienkijkanchai A, Wasant P.   World J Pediatr. 2014 Feb;10(1):64-8. doi: 10.1007/s12519-014-0454-4. Epub 2014 Jan 25

Mutation analysis in 54 propionic acidemia patients.

Kraus JP, Spector E, Venezia S, Estes P, Chiang PW, Creadon-Swindell G, Mullerleile S, de Silva L, Barth M, Walter M, Walter K, Meissner T, Lindnr M, Ensenauer R, Santr R, Bodamer OA, Baumgartner MR, Brunner-Krainz M, Karall D, Haase C, Knerr I, Marquardt T, Hennermann JB, Steinfeld R, Beblo S, Koch HG, Konstantopoulou V, Scholl-Burqi S, van Teeffelen-Heithoff A, Suormala T, Ugarte M, Sperl W, Superti-Furga A, Schwab KO, Grunert SC, Sass JO.              J Inherit Metab Dis. 2011 Oct 27. [Epub ahead of print]

Sass JO, Hofmann M, Skladal D, Mayatepek E, Schwahn B, Sperl W.

Propionic acidemia revisited: a workshop report.
Clin Pediatr (Phila). 2004 Nov-Dec;43(9):837-43.

Jiang H, Rao KS, Yee VC, Kraus JP.

Characterization of four variant forms of human propionyl-CoA carboxylase expressed in Escherichia coli.
J Biol Chem. 2005 Jul 29;280(30):27719-27.

Sloane V, Waldrop GL.

Kinetic characterization of mutations found in propionic acidemia and methylcrotonylglycinuria: evidence for cooperativity in biotin carboxylase.
J Biol Chem. 2004 Apr 16;279(16):15772-8.

Chloupkova M, Maclean KN, Alkhateeb A, Kraus JP.

Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes expressed in Escherichia coli. Hum Mutat. 2002 Jun;19(6):629-40.

Kelson TL, Ohura T, Kraus JP.

Chaperonin-mediated assembly of wild-type and utant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli.

Hum Mol Genet. 1996 Mar;5(3):331-7.

Desviat LR, Sanchez-Alcudia R, Pérez B, Pérez-Cerdá C, Navarrete R, Vijzelaar R, Ugarte M.  High frequency of large genomic deletions in the PCCA gene causing propionic acidemia.

Mol Genet Metab. 2009 Jan 19. [Epub ahead of print)

Kaya N, Al-Owain M, Albakheet A, Colak D, Al-Odaib A, Imtiaz F, Coskun S, Al-Sayed M, Al-Hassnan Z, Al-Zaidan H, Meyer B, Ozand P.

Array comparative genomic hybridization (aCGH) reveals the largest novel deletion in PCCA found in a Saudi family with propionic acidemia.

Eur J Med Genet. 2008 Aug 26. [Epub ahead of print]

 

Ugarte M, Aguado C, Desviat LR, Sanchez-Alcudia R, Rincon A, Perez B.

Propionic and Methylmalonic Acidemia: Antisense Therapeutics for Intronic ariations Causing Aberrantly Spliced Messenger RNA.
Am J Hum Genet. 2007 Oct 26;81(6)

Clavero S, Pérez B, Rincón A, Ugarte M, Desviat LR.

Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes.
Hum Genet. 2004 Aug;115(3):239-47.

Pérez B, Desviat LR, Rodríguez-Pombo P, Clavero S, Navarrete R, Perez-Cerdá C, Ugarte M.

Propionic acidemia: identification of twenty-four novel mutations in Europe and North America. Mol Genet Metab. 2003 Jan;78(1):59-67.

Pérez-Cerdá C, Clavero S, Pérez B, Rodríguez-Pombo P, Desviat LR, Ugarte M.

Functional analysis of PCCB mutations causing propionic acidemia based on expression studies in deficient human skin fibroblasts.
Biochim Biophys Acta. 2003 May 20;1638(1):43-9.

Clavero S, Martínez MA, Pérez B, Pérez-Cerdá C, Ugarte M, Desviat LR.

Functional characterization of PCCA mutations causing propionic acidemia.
Biochim Biophys Acta. 2002 Nov 20;1588(2):119-25.

Campeau E, Desviat LR, Leclerc D, Wu X, Pérez B, Ugarte M, Gravel RA.

Structure of the PCCA gene and distribution of mutations causing propionic acidemia.
Mol Genet Metab. 2001 Sep-Oct;74(1-2):238-47.

Ugarte M, Pérez-Cerdá C,Rodríguez-Pombo P,Desviat LR, Pérez B, Richard E, uro S, Campeau E, Ohura T, Gravel RA.

Overview of mutations in the PCCA and PCCB genes causing propionic acidemia.

Hum Mutat. 1999;14(4):275-82. 

Prenatal Diagnosis

Bustamante-Aragones A, Pérez-Cerdá C, Pérez B, Rodriguez de Alba M, Ugarte M, Ramos C.

Prenatal diagnosis in maternal plasma of a fetal mutation causing propionic acidemia.

Mol Genet Metab. 2008 Jul 1. (Epub ahead of print)

Inoue Y, Ohse M, Shinka T, Kuhara T

Prenatal diagnosis of propionic acidemia by measuring methylcitric acid in dried amniotic fluid on filter paper using GCMS.

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Mar 4.

Aramaki S, Lehotay D, Nyhan WL, Macleod PM, Sweetman L.

Methylcitrate in maternal urine during a pregnancy with a fetus affected with propionic acidaemia.

Inherit Metab Dis. 1989;12(1):86-8.