Journal of Inherited Metabolic Disease

, Volume 39, Issue 2, pp 231–241 | Cite as

Behavioural and emotional problems, intellectual impairment and health-related quality of life in patients with organic acidurias and urea cycle disorders

  • Dagmar Jamiolkowski
  • Stefan Kölker
  • Esther M. Glahn
  • Ivo Barić
  • Jiri Zeman
  • Matthias R. Baumgartner
  • Chris Mühlhausen
  • Angels Garcia-Cazorla
  • Florian Gleich
  • Gisela Haege
  • Peter BurgardEmail author
  • on behalf of the E-IMD consortium
Original Article



Organic acidurias (OADs) and urea cycle disorders (UCDs) are inborn metabolic disorders with a risk for acute and chronic metabolic decompensation resulting in impairments of the central nervous system and other organ systems. So far, there is no systematic study of intellectual functioning, behavioural/emotional problems and health-related quality of life (HRQoL), and how these domains are connected.


Data of 152 patients with OADs (n = 100) and UCDs (n = 52) from the European Registry and Network of intoxication type Metabolic Diseases (E-IMD) using standardized instruments were compared with normative data.


Behavioural/emotional problems are increased in OADs or UCDs patients by a factor of 2.5 (3.0), in female asymptomatic carriers of X-linked inherited UCD ornithine transcarbamylase deficiency (fasOTCD) by a factor of 1.5. All groups show similar patterns of behavioural/emotional problems, not different from epidemiological data. Mental disability (IQ ≤ 70) was found in 31 % of OAD, 43 % of UCD, but not in fasOTCD subjects. HRQoL was decreased in the physical domain, but in the normal range. Behavioural/emotional problems were significantly associated with intellectual functioning (OR = 6.24, 95 %CI: 1.39–27.99), but HRQoL was independent from both variables.


Patients with OADs and UCDs show increased frequencies of mental disability and behavioural/emotional problems. Profiles of behavioural/emotional problems were similar to epidemiological data. Intellectual disability and behavioural/emotional problems were strongly associated. Patients’ HRQoL was in the normal range, possibly compensated by coping strategies of their families. Diagnostics and clinical care of OAD/UCD patients should be improved regarding behavioural/emotional, intellectual and quality of life aspects.


Attention Deficit Hyperactivity Disorder Intellectual Disability Disease Group Intellectual Functioning Characteristic Component 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Arginase 1


Argininosuccinate lyase


Argininosuccinate synthetase


Carbamylphosphate synthetase 1


European registry and network for intoxication type metabolic diseases


Female asymptomatic OTC deficiency carrier


Female symptomatic OTC deficiency carrier


Glutaric aciduria type 1

HHH syndrome

Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome


Health-related quality of life


Inherited metabolic disease


Isovaleric aciduria


Mental illness


Methylmalonic aciduria


Male OTC deficiency


N-acetylglutamate synthase


Organic aciduria


Ornithine transcarbamylase deficiency


Propionic aciduria


Urea cycle disorder



This publication arises from the project “European registry and network for intoxication type metabolic diseases (E-IMD)” (EAHC no 2010 12 01) which has received funding from the European Union, in the framework of the Health Programme. We thank the following colleagues who have contributed further data to this study: Jolanta Cegielska-Nolte, Warsaw; Persephone Augoustides-Savvopoulou, Thessaloniki; Luis Pena Quintana, Las Palmas De Gran Canaria; Anil Jalan, Mumbai. Collection of UCD data has also been generously supported by the Dietmar Hopp Stiftung St. Leon-Rot. Notably, we thank all patients and families for providing personal information without which this study would not have been possible.

Compliance with ethics guidelines

Conflict of interest


Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients or their legal guardians prior to being included in the study in countries where this was needed by law.


This publication arises from the project “European registry and network for intoxication type metabolic diseases” (E-IMD; EAHC no 2010 12 01) which has received funding from the European Union, in the framework of the Health Programme. After the end of the EU funding period the E-IMD patient registry has been sustained by funding from the Kindness-for-Kids Foundation (Munich, Germany). Data collection regarding patients with UCDs has been supported by the Dietmar Hopp Foundation (St- Leon-Rot, Germany). MRB is supported by radiz — Rare Disease Initiative Zurich, a clinical research priority program for rare diseases of the University of Zurich.

Supplementary material

10545_2015_9887_MOESM1_ESM.docx (191 kb)
ESM 1 (DOCX 190 kb)


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Copyright information

© SSIEM 2015

Authors and Affiliations

  • Dagmar Jamiolkowski
    • 1
  • Stefan Kölker
    • 1
  • Esther M. Glahn
    • 1
  • Ivo Barić
    • 2
  • Jiri Zeman
    • 3
  • Matthias R. Baumgartner
    • 4
    • 5
    • 6
  • Chris Mühlhausen
    • 7
  • Angels Garcia-Cazorla
    • 8
  • Florian Gleich
    • 1
  • Gisela Haege
    • 1
  • Peter Burgard
    • 1
    Email author
  • on behalf of the E-IMD consortium
  1. 1.Centre for Paediatric and Adolescent Medicine, Division for Neuropaediatrics and Metabolic MedicineHeidelberg University HospitalHeidelbergGermany
  2. 2.Department of PediatrcisUniversity Hospital Center Zagreb & University of Zagreb, School of MedicineZagrebCroatia
  3. 3.Department of Pediatrics, General Faculty Hospital and First Faculty of MedicineCharles University in PraguePragueCzech Republic
  4. 4.Division of Metabolism and Children’s Research CentreUniversity Children’s HospitalZurichSwitzerland
  5. 5.Radiz – Rare Disease Initiative Zurich, Clinical Research Priority ProgramUniversity of ZurichZurichSwitzerland
  6. 6.Zurich Centre for Integrative Human PhysiologyUniversity of ZurichZurichSwitzerland
  7. 7.University Children’s Hospital, University Medical Centre Hamburg-EppendorfHamburgGermany
  8. 8.Hospital San Joan de Deu, Servicio de Neurologia and CIBERER, ISCIIIBarcelonaSpain

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