BACKGROUND: The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific. AIMS/METHODS: To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry. RESULTS: We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients (69 %) were symptomatic. The majority of them (n = 463) presented with acute metabolic crisis during (n = 220) or after the newborn period (n = 243) frequently demonstrating impaired consciousness, vomiting and/or muscular hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency, unexpectedly low in male OTC deficiency, and least frequently in GA1 and female OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency (male and female), hyperammonemia was more severe in metabolic crises during than after the newborn period, whereas metabolic acidosis tended to be more severe in MMA and PA patients with late onset of symptoms. Symptomatic patients without metabolic crises (n = 94) often presented with a movement disorder, mental retardation, epilepsy and psychiatric disorders (the latter in UCD only). CONCLUSIONS: The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis.

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

1st Pediatric Department Metabolic Laboratory General Hospital of Thessaloniki 'Hippocration' Thessaloniki Greece

Birmingham Children's Hospital NHS Foundation Trust Steelhouse Lane Birmingham B4 6NH UK

Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte Hôpital Jeanne de Flandre Lille France

Centre de Référence des Maladies Héréditaires du Métabolisme Service de Neurologie Hôpital d'Enfants CHU Timone Marseilles France

Centre for Inherited Metabolic Diseases Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Charles Dent Metabolic Unit National Hospital for Neurology and Neurosurgery London UK

Children's National Medical Center 111 Michigan Avenue N W Washington DC 20010 USA

Clinic for Pediatrics 1 Inherited Metabolic Disorders Medical University of Innsbruck Innsbruck Austria

Department of General Pediatrics Division of Inherited Metabolic Diseases University Children's Hospital Heidelberg Im Neuenheimer Feld 430 D 69120 Heidelberg Germany

Department of Laboratory Diagnostics The Children's Memorial Health Institute Warsaw Poland

Department of Pediatrics Academisch Medisch Centrum Amsterdam Netherlands

Department of Pediatrics Kumamoto University Hospital Kumamoto City Japan

Division of Metabolism and Children's Research Centre University Children's Hospital Zurich Steinwiesstraße 75 CH 8032 Zurich Switzerland

Erasmus MC Sophia Kinderziekenhuis Erasmus Universiteit Rotterdam Rotterdam Netherlands

Evelina Children's Hospital St Thomas' Hospital London UK

Hôpital Necker Enfants Malades Assistance Publique Hôpitaux de Paris Reference Center for Inherited Metabolic Disease Necker Enfants Malades University Hospital and IMAGINE Institute Paris France

Hôpital Robert Debré Université de Paris Paris France

Hospital Materno Infantil Málaga Spain

Hospital Universitario Materno Infantil de Canarias Unit of Pediatric Gastroenterology Hepatology and Nutrition University of Las Palmas de Gran Canaria Las Palmas de Gran Canaria Spain

Inborn Metabolic Disease Unit Hospital Virgen de la Arrixaca de Murcia El Palmar Spain

Institute of Mother and Child Care Alfred Rusescu Bucharest Romania

Klinik für Kinder und Jugendmedizin Universitätsklinikum Hamburg Eppendorf Hamburg Germany

Manchester Academic Health Science Centre Willink Biochemical Genetics Unit Genetic Medicine University of Manchester Manchester UK

Metabolic Unit Department of Pediatrics Hospital Clinico Universitario de Santiago de Compostela Santiago de Compostela Spain

Metabolic Unit Great Ormond Street Hospital and Institute for Child Health University College London London UK

N 1 R M A N Om Rachna Society Vashi Navi Mumbai Mumbai India

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

Screening Department Institute of Mother and Child Warsaw Poland

Service Gastroentérologie and Hépatologie Pédiatrique Cliniques Universitaires St Luc Université Catholique de Louvain Bruxelles Belgium

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

U O C Malattie Metaboliche Ereditarie Azienda Ospedaliera di Padova Padova Italy

U O C Patologia Metabolica Ospedale Pediatrico Bambino Gésu Rome Italy

Unidade de Doenças Metabólicas Serviço de Pediatria Hospital de S João EPE Porto Portugal

University Hospital Center Zagreb Zagreb Croatia

University Hospital Vrije Universiteit Brussel Bruxelles Belgium

Erratum v

J Inherit Metab Dis. 2015 Nov;38(6):1155-6. doi: 10.1007/s10545-015-9867-z. PubMed   Cazorla, Angeles Garcia [corrected to Garcia-Cazorla, Angeles]

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