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.

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

Department of Pediatrcis University Hospital Center Zagreb and University of Zagreb School of Medicine Zagreb Croatia

Department of Pediatrics General Faculty Hospital and 1st Faculty of Medicine Charles University Prague Prague Czech Republic

Division of Metabolism and Children's Research Centre University Children's Hospital Zurich Switzerland

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

Radiz Rare Disease Initiative Zurich Clinical Research Priority Program University of Zurich Zurich Switzerland

University Children's Hospital University Medical Centre Hamburg Eppendorf Martinistrasse 52 20246 Hamburg Germany

Zurich Centre for Integrative Human Physiology University of Zurich Zurich Switzerland

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