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J Inherit Metab Dis. 2015 Nov;38(6):1041-57. doi: 10.1007/s10545-015-9839-3. Epub 2015 Apr 15.

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation.

Author information

1
Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany. Stefan.Koelker@med.uni-heidelberg.de.
2
Servicio de Neurologia and CIBERER, ISCIII, Hospital San Joan de Deu, Barcelona, Spain.
3
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.
4
Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
5
U.O.C. Malattie Metaboliche Ereditarie, Azienda Ospedaliera di Padova, Padova, Italy.
6
Screening Department, Institute of Mother and Child, Warsaw, Poland.
7
Department of Pediatrics, Academisch Medisch Centrum, Amsterdam, Netherlands.
8
Unidade de Doenças Metabólicas, Serviço de Pediatria, Hospital de S. João, EPE, Porto, Portugal.
9
First Faculty of Medicine, Charles University and General University of Prague, Prague, Czech Republic.
10
U.O.C. Patologia Metabolica, Ospedale Pediatrico Bambino Gésu, Rome, Italy.
11
School of Medicine, University Hospital Center Zagreb and University of Zagreb, Zagreb, Croatia.
12
Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.
13
1st Pediatric Department, Metabolic Laboratory, General Hospital of Thessaloniki 'Hippocration', Thessaloniki, Greece.
14
Institute of Mother and Child Care "Alfred Rusescu", Bucharest, Romania.
15
Division of Metabolism and Children's Research Centre, University Children's Hospital Zurich, Steinwiesstraße 75, CH-8032, Zurich, Switzerland.
16
Hospital Materno-Infantil (HRU Carlos Haya), Málaga, Spain.
17
Centre de Référence des Maladies Héréditaires du Métabolisme, Service de Neurologie, Hôpital d'Enfants, CHU Timone, Marseilles, France.
18
Birmingham Children's Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH, UK.
19
Children's National Medical Center, 111 Michigan Avenue, N.W., Washington, DC, 20010, USA.
20
Metabolic Unit, Department of Pediatrics, Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
21
University Hospital Vrije Universiteit Brussel, Bruxelles, Belgium.
22
Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Hôpital Jeanne de Flandre, Lille, France.
23
Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
24
Department of Laboratory Diagnostics, The Children's Memorial Health Institute, Warsaw, Poland.
25
Metabolic Unit Great Ormond Street Hospital and Institute for Child Health, University College London, London, UK.
26
N.I.R.M.A.N., Om Rachna Society, Vashi, Navi Mumbai, Mumbai, India.
27
Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
28
Department of Pediatrics, Kumamoto University Hospital, Kumamoto City, Japan.
29
Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
30
Hôpital Robert Debré, Université de Paris, Paris, France.
31
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.
32
University Hospital Center Zagreb, Zagreb, Croatia.
33
Service Gastroentérologie and Hépatologie Pédiatrique, Cliniques Universitaires St Luc, Université Catholique de Louvain, Bruxelles, Belgium.
34
Evelina Children's Hospital, St Thomas' Hospital, London, UK.
35
Inborn Metabolic Disease Unit, Hospital Virgen de la Arrixaca de Murcia, El Palmar, Spain.
36
Manchester Academic Health Science Centre, Willink Biochemical Genetics Unit, Genetic Medicine, University of Manchester, Manchester, UK.
37
Erasmus MC-Sophia Kinderziekenhuis, Erasmus Universiteit Rotterdam, Rotterdam, Netherlands.

Abstract

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.

PMID:
25875215
DOI:
10.1007/s10545-015-9839-3
[Indexed for MEDLINE]

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