Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders
| Autor: | Mehdi Oualha, Valérie Barbier, Bernadette Chadefaux-Vekemans, Aude Servais, Célina Roda, Guy Touati, Anaïs Brassier, Laurent Dupic, Marie-Thérèse Abi-Warde, Coraline Grisel, Clément Pontoizeau, Anna Kaminska, Vassili Valayannopoulos, Monika Eisermann, Carole Hennequin, Patricia Vignolo-Diard, Chris Ottolenghi, Pascale de Lonlay, Alice Kuster, Florence Habarou, Nathalie Boddaert, Fabrice Lesage, Jean-Baptiste Arnoux |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Urea cycle disorder Developmental Disabilities Endocrinology Diabetes and Metabolism Carbamoyl-Phosphate Synthase (Ammonia) Ornithine transcarbamylase Status epilepticus Argininosuccinate Synthase 030105 genetics & heredity Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Ammonia Intellectual Disability Internal medicine Infant Mortality Intellectual disability Genetics medicine Humans Age of Onset Urea Cycle Disorders Inborn Molecular Biology Survival rate Ornithine Carbamoyltransferase Retrospective Studies Coma business.industry Infant Newborn Area under the curve Infant Hyperammonemia medicine.disease Female France medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Molecular Genetics and Metabolism. 130:110-117 |
| ISSN: | 1096-7192 |
| Popis: | Purpose We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. Methods We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. Results We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. Conclusion UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies. |
| Databáze: | OpenAIRE |
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