BACKGROUND: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. AIMS: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. RESULTS: Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. CONCLUSIONS: Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

• MeSH
• argininjantarová acidurie diagnóza   MeSH
• chronické selhání ledvin komplikace   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• glutaryl-CoA-dehydrogenasa nedostatek   MeSH
• játra metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické nemoci mozku diagnóza   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc z nedostatku ornithinkarbamoyltransferázy diagnóza   MeSH
• novorozenec MeSH
• novorozenecký screening MeSH
• předškolní dítě MeSH
• propionová acidemie diagnóza   MeSH
• registrace MeSH
• senioři MeSH
• vrozené poruchy cyklu močoviny diagnóza   MeSH
• vrozené poruchy metabolismu aminokyselin diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• glutaryl-CoA-dehydrogenasa MeSH

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.

• MeSH
• dítě MeSH
• dospělí MeSH
• glutaryl-CoA-dehydrogenasa nedostatek   MeSH
• hyperamonemie diagnóza   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mentální retardace MeSH
• metabolické nemoci mozku diagnóza   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc z nedostatku ornithinkarbamoyltransferázy diagnóza   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• registrace MeSH
• senioři MeSH
• vrozené poruchy cyklu močoviny diagnóza   MeSH
• vrozené poruchy metabolismu aminokyselin diagnóza   MeSH
• zvracení MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• glutaryl-CoA-dehydrogenasa MeSH