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

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

ARG1:

Arginase 1

ASL:

Argininosuccinate lyase

ASS:

Argininosuccinate synthetase

CPS1:

Carbamylphosphate synthetase 1

E-IMD:

European registry and network for intoxication type metabolic diseases

fasOTCD:

Female asymptomatic OTC deficiency carrier

fsOTCD:

Female symptomatic OTC deficiency carrier

GA1:

Glutaric aciduria type 1

HHH syndrome:

Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome

HRQoL:

Health-related quality of life

IMD:

Inherited metabolic disease

IVA:

Isovaleric aciduria

MI:

Mental illness

MMA:

Methylmalonic aciduria

mOTCD:

Male OTC deficiency

NAGS:

N-acetylglutamate synthase

OAD:

Organic aciduria

OTC:

Ornithine transcarbamylase deficiency

PA:

Propionic aciduria

UCD:

Urea cycle disorder

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Acknowledgments

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

ᅟ

Conflict of interest

None.

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.

Funding

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.

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Authors and Affiliations

  1. Centre for Paediatric and Adolescent Medicine, Division for Neuropaediatrics and Metabolic Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany

    Dagmar Jamiolkowski, Stefan Kölker, Esther M. Glahn, Florian Gleich, Gisela Haege & Peter Burgard

  2. Department of Pediatrcis, University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia

    Ivo Barić

  3. Department of Pediatrics, General Faculty Hospital and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    Jiri Zeman

  4. Division of Metabolism and Children’s Research Centre, University Children’s Hospital, Zurich, Switzerland

    Matthias R. Baumgartner

  5. Radiz – Rare Disease Initiative Zurich, Clinical Research Priority Program, University of Zurich, Zurich, Switzerland

    Matthias R. Baumgartner

  6. Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

    Matthias R. Baumgartner

  7. University Children’s Hospital, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Chris Mühlhausen

  8. Hospital San Joan de Deu, Servicio de Neurologia and CIBERER, ISCIII, Barcelona, Spain

    Angels Garcia-Cazorla

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  1. Dagmar Jamiolkowski
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  2. Stefan Kölker
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  3. Esther M. Glahn
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  4. Ivo Barić
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  7. Chris Mühlhausen
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  8. Angels Garcia-Cazorla
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  9. Florian Gleich
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  10. Gisela Haege
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  11. Peter Burgard
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Correspondence to Peter Burgard.

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Communicated by: Robert Steiner

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Jamiolkowski, D., Kölker, S., Glahn, E.M. et al. Behavioural and emotional problems, intellectual impairment and health-related quality of life in patients with organic acidurias and urea cycle disorders. J Inherit Metab Dis 39, 231–241 (2016). https://doi.org/10.1007/s10545-015-9887-8

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  • DOI: https://doi.org/10.1007/s10545-015-9887-8

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