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The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation
Author(s) -
Kölker Stefan,
Cazorla Angeles Garcia,
Valayannopoulos Vassili,
Lund Allan M.,
Burlina Alberto B.,
SykutCegielska Jolanta,
Wijburg Frits A.,
Teles Elisa Leão,
Zeman Jiri,
DionisiVici Carlo,
Barić Ivo,
Karall Daniela,
AugoustidesSavvopoulou Persephone,
Aksglaede Lise,
Arnoux JeanBaptiste,
Avram Paula,
Baumgartner Matthias R.,
BlascoAlonso Javier,
Chabrol Brigitte,
Chakrapani Anupam,
Chapman Kimberly,
Saladelafont Elisenda Cortès,
Couce Maria L.,
Meirleir Linda,
Dobbelaere Dries,
Dvorakova Veronika,
Furlan Francesca,
Gleich Florian,
Gradowska Wanda,
Grünewald Stephanie,
Jalan Anil,
Häberle Johannes,
Haege Gisela,
Lachmann Robin,
Laemmle Alexander,
Langereis Eveline,
Lonlay Pascale,
Martinelli Diego,
Matsumoto Shirou,
Mühlhausen Chris,
Baulny Hélène Ogier,
Ortez Carlos,
PeñaQuintana Luis,
Ramadža Danijela Petković,
Rodrigues Esmeralda,
SchollBürgi Sabine,
Sokal Etienne,
Staufner Christian,
Summar Marshall L.,
Thompson Nicholas,
Vara Roshni,
Pinera Inmaculada Vives,
Walter John H.,
Williams Monique,
Burgard Peter
Publication year - 2015
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-015-9839-3
Subject(s) - urea cycle , ornithine transcarbamylase deficiency , medicine , hypotonia , hyperammonemia , pediatrics , metabolic acidosis , methylmalonic aciduria , newborn screening , metabolic disorder , encephalopathy , inborn error of metabolism , methylmalonic acid , gastroenterology , arginine , vitamin b12 , biology , biochemistry , amino acid
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.