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Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients

Sarah C Grünert1, Stephanie Müllerleile2, Linda De Silva2, Michael Barth1, Melanie Walter2, Kerstin Walter1, Thomas Meissner5, Martin Lindner6, Regina Ensenauer7, René Santer8, Olaf A Bodamer109, Matthias R Baumgartner11, Michaela Brunner-Krainz12, Daniela Karall13, Claudia Haase1415, Ina Knerr16, Thorsten Marquardt17, Julia B Hennermann18, Robert Steinfeld19, Skadi Beblo20, Hans-Georg Koch21, Vassiliki Konstantopoulou9, Sabine Scholl-Bürgi13, Agnes van Teeffelen-Heithoff17, Terttu Suormala22, Wolfgang Sperl23, Jan P Kraus24, Andrea Superti-Furga14, Karl Otfried Schwab1 and Jörn Oliver Sass23*

Author Affiliations

1 Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Freiburg, Germany

2 Labor für Klinische Biochemie und Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Freiburg, Germany

3 Klinische Chemie & Biochemie, Universitäts-Kinderspital Zürich, Steinwiesstrasse 75, 8032, Zürich, Switzerland

4 Present address: University of Lausanne, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

5 Klinik für Allgemeine Pädiatrie, Neonatologie und Kinderkardiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

6 Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Heidelberg, Heidelberg, Germany

7 Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany

8 Kinderklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

9 Allgemeine Pädiatrie, AKH, Medizinische Universität Wien, Wien, Austria

10 Present address: Department of Human Genetics, Division of Clinical and Translational Genetics and Genomics; Miller School of Medicine, University of Miami, Florida, USA

11 Stoffwechsel und Molekulare Pädiatrie, Universitäts-Kinderspital Zürich, Zürich, Switzerland

12 Universitätsklinikum für Kinder- und Jugendheilkunde, Medizinische Universität Graz, Graz, Austria

13 Universitätsklinik für Kinder- und Jugendheilkunde, Medizinische Universität Innsbruck, Innsbruck, Austria

14 Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena, Jena, Germany

15 Present address: Helios Klinikum Erfurt, Klinik für Kinder und Jugendmedizin, Erfurt, Germany

16 National Centre for Inherited Metabolic Disorders, Children’s University Hospital Dublin, Dublin, Ireland

17 Allgemeine Pädiatrie, Universitätskinderklinik Münster, Münster, Germany

18 Klinik für Pädiatrie m. S. Endokrinologie, Gastroenterologie und Stoffwechselmedizin, Charité Universitätsmedizin Berlin, Berlin, Germany

19 Kinderklinik, Georg-August-Universität Göttingen, Göttingen, Germany

20 Universitätsklinikum für Kinder und Jugendliche, Leipzig, Germany

21 Klinik für Kinder- und Jugendmedizin, Braunschweig, Germany

22 Universitäts-Kinderspital Basel, Basel, Switzerland

23 Paracelsus Medizinische Privatuniversität, Universitätsklinikum für Kinder- und Jugendheilkunde, Salzburg, Austria

24 Department of Pediatrics, University of Colorado, Aurora, USA

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Orphanet Journal of Rare Diseases 2013, 8:6  doi:10.1186/1750-1172-8-6

Published: 10 January 2013



Propionic acidemia is an inherited disorder caused by deficiency of propionyl-CoA carboxylase. Although it is one of the most frequent organic acidurias, information on the outcome of affected individuals is still limited.

Study design/methods

Clinical and outcome data of 55 patients with propionic acidemia from 16 European metabolic centers were evaluated retrospectively. 35 patients were diagnosed by selective metabolic screening while 20 patients were identified by newborn screening. Endocrine parameters and bone age were evaluated. In addition, IQ testing was performed and the patients’ and their families’ quality of life was assessed.


The vast majority of patients (>85%) presented with metabolic decompensation in the neonatal period. Asymptomatic individuals were the exception. About three quarters of the study population was mentally retarded, median IQ was 55. Apart from neurologic symptoms, complications comprised hematologic abnormalities, cardiac diseases, feeding problems and impaired growth. Most patients considered their quality of life high. However, according to the parents’ point of view psychic problems were four times more common in propionic acidemia patients than in healthy controls.


Our data show that the outcome of propionic acidemia is still unfavourable, in spite of improved clinical management. Many patients develop long-term complications affecting different organ systems. Impairment of neurocognitive development is of special concern. Nevertheless, self-assessment of quality of life of the patients and their parents yielded rather positive results.

Propionic acidemia; Branched-chain amino acids; Outcome; Quality of life; Clinical course; Physical development; Neurocognitive development; IQ; Long-term complications; Propionyl-coenzyme A carboxylase deficiency