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Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013

BACKGROUND: Urea cycle disorders (UCDs) are rare inherited metabolic defects of ammonia detoxification. In about half of patients presenting with a UCD, the first symptoms appear within a few days after birth. These neonatal onset patients generally have a severe defect of urea cycle function and th...

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Autores principales: Unsinn, Caroline, Das, Anibh, Valayannopoulos, Vassili, Thimm, Eva, Beblo, Skadi, Burlina, Alberto, Konstantopoulou, Vassiliki, Mayorandan, Sebene, de Lonlay, Pascale, Rennecke, Jörg, Derbinski, Jens, Hoffmann, Georg F., Häberle, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991093/
https://www.ncbi.nlm.nih.gov/pubmed/27538463
http://dx.doi.org/10.1186/s13023-016-0493-0
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author Unsinn, Caroline
Das, Anibh
Valayannopoulos, Vassili
Thimm, Eva
Beblo, Skadi
Burlina, Alberto
Konstantopoulou, Vassiliki
Mayorandan, Sebene
de Lonlay, Pascale
Rennecke, Jörg
Derbinski, Jens
Hoffmann, Georg F.
Häberle, Johannes
author_facet Unsinn, Caroline
Das, Anibh
Valayannopoulos, Vassili
Thimm, Eva
Beblo, Skadi
Burlina, Alberto
Konstantopoulou, Vassiliki
Mayorandan, Sebene
de Lonlay, Pascale
Rennecke, Jörg
Derbinski, Jens
Hoffmann, Georg F.
Häberle, Johannes
author_sort Unsinn, Caroline
collection PubMed
description BACKGROUND: Urea cycle disorders (UCDs) are rare inherited metabolic defects of ammonia detoxification. In about half of patients presenting with a UCD, the first symptoms appear within a few days after birth. These neonatal onset patients generally have a severe defect of urea cycle function and their survival and outcome prognoses are often limited. To understand better the current situation of neonatal onset in UCDs, we have performed a multicentre, retrospective, non-interventional case series study focussing on the most severe UCDs, namely defects of carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (ASS). METHODS AND RESULTS: Data of 63 patients were collected (27 patients with ASS deficiency, 23 patients with OTC deficiency, and 12 patients with CPS1 deficiency, one patient definite diagnosis not documented). The majority of patients (43/63, 68 %) had an initial ammonia concentration exceeding 500 μmol/L (normal < 100), of which most (26/43, 60.5 %) were also encephalopathic and were treated with hemodialysis. In patients surviving the initial crisis, recurrence of hyperammonemic events within the first 1.5 years of life occurred frequently (mean 3.6 events, range 0–20). Of all patients, 16 (25.4 %) died during or immediately after the neonatal period. CONCLUSION: We observed in this cohort of neonatal onset UCD patients a high rate of initial life-threatening hyperammonemia and a high risk of recurrence of severe hyperammonemic crises. These corresponded to a high mortality rate during the entire study period (30.2 %) despite the fact that patients were treated in leading European metabolic centers. This underlines the need to critically re-evaluate the current treatment strategies in these patients.
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spelling pubmed-49910932016-08-20 Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013 Unsinn, Caroline Das, Anibh Valayannopoulos, Vassili Thimm, Eva Beblo, Skadi Burlina, Alberto Konstantopoulou, Vassiliki Mayorandan, Sebene de Lonlay, Pascale Rennecke, Jörg Derbinski, Jens Hoffmann, Georg F. Häberle, Johannes Orphanet J Rare Dis Research BACKGROUND: Urea cycle disorders (UCDs) are rare inherited metabolic defects of ammonia detoxification. In about half of patients presenting with a UCD, the first symptoms appear within a few days after birth. These neonatal onset patients generally have a severe defect of urea cycle function and their survival and outcome prognoses are often limited. To understand better the current situation of neonatal onset in UCDs, we have performed a multicentre, retrospective, non-interventional case series study focussing on the most severe UCDs, namely defects of carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (ASS). METHODS AND RESULTS: Data of 63 patients were collected (27 patients with ASS deficiency, 23 patients with OTC deficiency, and 12 patients with CPS1 deficiency, one patient definite diagnosis not documented). The majority of patients (43/63, 68 %) had an initial ammonia concentration exceeding 500 μmol/L (normal < 100), of which most (26/43, 60.5 %) were also encephalopathic and were treated with hemodialysis. In patients surviving the initial crisis, recurrence of hyperammonemic events within the first 1.5 years of life occurred frequently (mean 3.6 events, range 0–20). Of all patients, 16 (25.4 %) died during or immediately after the neonatal period. CONCLUSION: We observed in this cohort of neonatal onset UCD patients a high rate of initial life-threatening hyperammonemia and a high risk of recurrence of severe hyperammonemic crises. These corresponded to a high mortality rate during the entire study period (30.2 %) despite the fact that patients were treated in leading European metabolic centers. This underlines the need to critically re-evaluate the current treatment strategies in these patients. BioMed Central 2016-08-19 /pmc/articles/PMC4991093/ /pubmed/27538463 http://dx.doi.org/10.1186/s13023-016-0493-0 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Unsinn, Caroline
Das, Anibh
Valayannopoulos, Vassili
Thimm, Eva
Beblo, Skadi
Burlina, Alberto
Konstantopoulou, Vassiliki
Mayorandan, Sebene
de Lonlay, Pascale
Rennecke, Jörg
Derbinski, Jens
Hoffmann, Georg F.
Häberle, Johannes
Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
title Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
title_full Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
title_fullStr Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
title_full_unstemmed Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
title_short Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
title_sort clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991093/
https://www.ncbi.nlm.nih.gov/pubmed/27538463
http://dx.doi.org/10.1186/s13023-016-0493-0
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