Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience
Aim:Urea cycle disorders (UCD) still have poor neurological outcomes despite early diagnosis and treatment. We aimed to present the neurological outcomes of UCD patients and to determine the main simple and accessible factors affecting these outcomes.Materials and Methods:This was a descriptive cros...
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| Format: | Article |
| Language: | English |
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Galenos Yayinevi
2023-09-01
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| Series: | Journal of Pediatric Research |
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http://jpedres.org/archives/archive-detail/article-preview/evaluation-of-the-neurodevelopmental-status-for-ur/62076
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| author | Ayşe Ergül Bozacı Emine Göksoy Aysel Tekmenuray Ünal Hatice Mutlu Albayrak İbrahim Taş Berat Kanar Mehmet Nuri Özbek Melis Köse |
| author_facet | Ayşe Ergül Bozacı Emine Göksoy Aysel Tekmenuray Ünal Hatice Mutlu Albayrak İbrahim Taş Berat Kanar Mehmet Nuri Özbek Melis Köse |
| author_sort | Ayşe Ergül Bozacı |
| collection | DOAJ |
| description | Aim:Urea cycle disorders (UCD) still have poor neurological outcomes despite early diagnosis and treatment. We aimed to present the neurological outcomes of UCD patients and to determine the main simple and accessible factors affecting these outcomes.Materials and Methods:This was a descriptive cross-sectional study conducted in two pediatric metabolism centers on 29 patients from 25 unrelated families who were diagnosed and followed with UCD based on clinical presentation, neurological parameters, biochemical measurements, and molecular analysis.Results:Within the study population, the most common diagnosis was argininosuccinate synthase deficiency in 13 (44.82%) patients, followed by N-acetylglutamate synthase deficiency in five patients (17.24%), ornithine transcarbamylase deficiency in four patients (13.79%), arginase 1 deficiency in three patients (10.34%), carbamoyl phosphate synthase 1 deficiency in three patients (10.34%), and argininosuccinate lyase deficiency in one patient (3.44%). Peak ammonia levels were observed to be significantly higher in those patients with delayed milestones and patients who had Denver II <-2 standard deviation score results (p=0.032, p=0.026). Effect sizes were large in both groups. Delayed milestones were noted in 17 (94.4%) of the cases with peak ammonia >500 μmol/L (n=18). Those patients with abnormal neurological parameters had a significantly higher mean number of hyperammonemic episodes per year. Extracorporeal detoxification was given to eight patients, in combination with therapeutic hypothermia in two patients. Rapid regression was observed in brain edema in those who underwent therapeutic hypothermia.Conclusion:Our study emphasizes the effect of peak ammonia levels and the frequency of hyperammonemic episodes on neurological outcomes. There were still poor neurocognitive outcomes despite extracorporeal detoxification. This highlights the need to reassess current treatment strategies, including the threshold for starting extracorporeal detoxification if ammonia levels exceed 500 µmol/L. The use of therapeutic hypothermia by experienced teams may be promising due to its brain edema-reducing effects. |
| first_indexed | 2024-03-12T00:58:35Z |
| format | Article |
| id | doaj.art-e3748e19c3c44e969f25d57aa5af3721 |
| institution | Directory Open Access Journal |
| issn | 2147-9445 2587-2478 |
| language | English |
| last_indexed | 2024-03-12T00:58:35Z |
| publishDate | 2023-09-01 |
| publisher | Galenos Yayinevi |
| record_format | Article |
| series | Journal of Pediatric Research |
| spelling | doaj.art-e3748e19c3c44e969f25d57aa5af37212023-09-14T11:14:18ZengGalenos YayineviJournal of Pediatric Research2147-94452587-24782023-09-0110318219410.4274/jpr.galenos.2023.9699213049054Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical ExperienceAyşe Ergül Bozacı0Emine Göksoy1Aysel Tekmenuray Ünal2Hatice Mutlu Albayrak3İbrahim Taş4Berat Kanar5Mehmet Nuri Özbek6Melis Köse7 Diyarbakır Children’s Hospital, Clinic of Pediatric Nutrition and Metabolism, Diyarbakır, Turkey Gaziantep Cengiz Gökçek Obstetrics and Gynecology and Children Hospital, Clinic of Pediatric Nutrition and Metabolism, Gaziantep, Turkey University of Health Sciences Turkey, Diyarbakır Gaziyaşargil Training and Research Hospital, Clinic of Medical Genetics, Diyarbakır, Turkey Gaziantep Children’s Hospital, Clinic of Medical Genetics, Gaziantep, Turkey Diyarbakır Children’s Hospital, Clinic of Pediatric Nutrition and Metabolism, Diyarbakır, Turkey Diyarbakır Children’s Hospital, Clinic of Neonatology, Diyarbakır, Turkey Mardin Artuklu University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Mardin, Turkey The Children Hospital of Philadelphia, Clinic of Genetics, Mitochondrial Medicine Frontier Program, Philadelphia, USA Aim:Urea cycle disorders (UCD) still have poor neurological outcomes despite early diagnosis and treatment. We aimed to present the neurological outcomes of UCD patients and to determine the main simple and accessible factors affecting these outcomes.Materials and Methods:This was a descriptive cross-sectional study conducted in two pediatric metabolism centers on 29 patients from 25 unrelated families who were diagnosed and followed with UCD based on clinical presentation, neurological parameters, biochemical measurements, and molecular analysis.Results:Within the study population, the most common diagnosis was argininosuccinate synthase deficiency in 13 (44.82%) patients, followed by N-acetylglutamate synthase deficiency in five patients (17.24%), ornithine transcarbamylase deficiency in four patients (13.79%), arginase 1 deficiency in three patients (10.34%), carbamoyl phosphate synthase 1 deficiency in three patients (10.34%), and argininosuccinate lyase deficiency in one patient (3.44%). Peak ammonia levels were observed to be significantly higher in those patients with delayed milestones and patients who had Denver II <-2 standard deviation score results (p=0.032, p=0.026). Effect sizes were large in both groups. Delayed milestones were noted in 17 (94.4%) of the cases with peak ammonia >500 μmol/L (n=18). Those patients with abnormal neurological parameters had a significantly higher mean number of hyperammonemic episodes per year. Extracorporeal detoxification was given to eight patients, in combination with therapeutic hypothermia in two patients. Rapid regression was observed in brain edema in those who underwent therapeutic hypothermia.Conclusion:Our study emphasizes the effect of peak ammonia levels and the frequency of hyperammonemic episodes on neurological outcomes. There were still poor neurocognitive outcomes despite extracorporeal detoxification. This highlights the need to reassess current treatment strategies, including the threshold for starting extracorporeal detoxification if ammonia levels exceed 500 µmol/L. The use of therapeutic hypothermia by experienced teams may be promising due to its brain edema-reducing effects. http://jpedres.org/archives/archive-detail/article-preview/evaluation-of-the-neurodevelopmental-status-for-ur/62076 urea cycle disordershyperammonemiacitrullinemiainborn errors of metabolismtherapeutic hypothermia |
| spellingShingle | Ayşe Ergül Bozacı Emine Göksoy Aysel Tekmenuray Ünal Hatice Mutlu Albayrak İbrahim Taş Berat Kanar Mehmet Nuri Özbek Melis Köse Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience Journal of Pediatric Research urea cycle disorders hyperammonemia citrullinemia inborn errors of metabolism therapeutic hypothermia |
| title | Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience |
| title_full | Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience |
| title_fullStr | Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience |
| title_full_unstemmed | Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience |
| title_short | Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience |
| title_sort | evaluation of the neurodevelopmental status for urea cycle disorders based on clinical experience |
| topic | urea cycle disorders hyperammonemia citrullinemia inborn errors of metabolism therapeutic hypothermia |
| url |
http://jpedres.org/archives/archive-detail/article-preview/evaluation-of-the-neurodevelopmental-status-for-ur/62076
|
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