European Journal of Pediatrics

, Volume 173, Issue 7, pp 971–974 | Cite as

Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy

  • Alexander LaemmleEmail author
  • Christian Balmer
  • Carsten Doell
  • Jörn Oliver Sass
  • Johannes Häberle
  • Matthias R. Baumgartner
Case Report


Propionic acidemia (PA) is a rare autosomal recessive organic aciduria resulting from defects in propionyl-CoA-carboxylase (PCC), a key enzyme of intermediate energy metabolism. PA mostly manifests during the neonatal period, when affected newborns develop severe metabolic acidosis and hyperammonemia. We present a previously healthy teenager, who suffered from acute fatigue and breathlessness. The patient was tachycardic, displayed a precordial heave and a systolic murmur. Cardiac investigations revealed severe dilated cardiomyopathy (DCM). Biochemical work up led to the diagnosis of PA. Remarkably, this patient of consanguineous Hispanic origin was in a good general health condition before the acute onset of DCM. Diagnosis of PA was confirmed by enzymatic and molecular genetic analysis, the latter revealing a novel homozygous mutation in the PCCB gene (c.1229G > A; p.R410Q). Residual PCC enzyme activity of approximately 14 % of normal was detected in patient’s lymphocytes and fibroblasts, thereby providing a possible explanation for the hitherto asymptomatic phenotype. Conclusion: Isolated DCM, although rare, can be the leading and/or sole symptom of late-onset PA. Therefore, patients with DCM should receive a comprehensive diagnostic evaluation including selective screening for inborn errors of metabolism.


Propionic acidemia Dilated cardiomyopathy Propionyl-CoA carboxylase Organic aciduria 



Attention deficit and hyperactivity syndrome


Dilated cardiomyopathy




Propionic acidemia


Propionyl-CoA carboxylase subunits A and B



This work has been supported by radiz—Rare Disease Initiative Zurich, a clinical research priority program of the University of Zurich. We would like to thank Corinne Britschgi and Seraina Lutz for technical support with molecular genetic analysis of PCCB gene and PCC activity assays, respectively.

Conflict of interest



  1. 1.
    Baumgartner D, Scholl-Bürgi S, Sass JO, Sperl W, Schweigmann U, Stein JI, Karall D (2007) Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia. J Pediatr 150:192–197PubMedCrossRefGoogle Scholar
  2. 2.
    Fenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet A, Sly W, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, pp 2165–2190Google Scholar
  3. 3.
    Gallego-Villar L, Perez-Cerda C, Perez B, Abia D, Ugarte M, Richard E, Desviat LR (2012) Functional characterization of novel genotypes and cellular oxidative stress studies in propionic acidemia. J Inherit Metab Dis 36:731–740PubMedCrossRefGoogle Scholar
  4. 4.
    Grünert SC, Müllerleile S, De Silva L, Barth M, Walter M, Walter K, Meissner T, Lindner M, Ensenauer R, Santer 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-Bürgi S, van Teeffelen-Heithoff A, Suormala T, Sperl W, Kraus JP, Superti-Furga A, Schwab KO, Sass JO (2013) Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients. Orphanet J Rare Dis 8:6PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Lee TM, Addonizio LJ, Barshop BA, Chung WK (2009) Unusual presentation of propionic acidaemia as isolated cardiomyopathy. J Inherit Metab Dis 32(Suppl 1):S97–S101PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Mardach R, Verity MA, Cederbaum SD (2005) Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy. Mol Genet Metab 85:286–290PubMedCrossRefGoogle Scholar
  7. 7.
    Massoud AF, Leonard JV (1993) Cardiomyopathy in propionic acidaemia. Eur J Pediatr 152:441–445PubMedCrossRefGoogle Scholar
  8. 8.
    Nymark TB, Hovland A, Bjornstad H, Nielsen EW (2008) A young man with acute dilated cardiomyopathy associated with methylphenidate. Vasc Health Risk Manag 4:477–479PubMedCentralPubMedGoogle Scholar
  9. 9.
    Romano S, Valayannopoulos V, Touati G, Jais JP, Rabier D, de Keyzer Y, Bonnet D, de Lonlay P (2010) Cardiomyopathies in propionic aciduria are reversible after liver transplantation. J Pediatr 156:128–134PubMedCrossRefGoogle Scholar
  10. 10.
    Suormala T, Wick H, Bonjour JP, Baumgartner ER (1985) Rapid differential diagnosis of carboxylase deficiencies and evaluation for biotin-responsiveness in a single blood sample. Clin Chim Acta 145:151–162PubMedCrossRefGoogle Scholar
  11. 11.
    Yang X, Sakamoto O, Matsubara Y, Kure S, Suzuki Y, Aoki Y, Yamaguchi S, Takahashi Y, Nishikubo T, Kawaguchi C, Yoshioka A, Kimura T, Hayasaka K, Kohno Y, Iinuma K, Ohura T (2004) Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia. Mol Genet Metab 81:335–342PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Alexander Laemmle
    • 1
    • 5
    Email author
  • Christian Balmer
    • 2
    • 5
  • Carsten Doell
    • 3
  • Jörn Oliver Sass
    • 4
    • 5
  • Johannes Häberle
    • 1
    • 5
  • Matthias R. Baumgartner
    • 1
    • 5
  1. 1.Division of Metabolic DiseasesUniversity Children`s HospitalZurichSwitzerland
  2. 2.Division of CardiologyUniversity Children`s HospitalZurichSwitzerland
  3. 3.Division of Neonatology and Paediatric Intensive CareUniversity Children`s HospitalZurichSwitzerland
  4. 4.Division of Clinical Chemistry & BiochemistryUniversity Children`s HospitalZurichSwitzerland
  5. 5.Children’s Research CenterUniversity Children`s HospitalZurichSwitzerland

Personalised recommendations