Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F16%3A10327966" target="_blank" >RIV/00064165:_____/16:10327966 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/16:10327966

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s10545-016-9938-9" target="_blank" >http://dx.doi.org/10.1007/s10545-016-9938-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10545-016-9938-9" target="_blank" >10.1007/s10545-016-9938-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders

Popis výsledku v původním jazyce

Background Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation. Aims Determining the effect of diagnostic and therapeutic interventions on the neurological outcome. Methods Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry. Results About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 mu mol/L) best predicted the neurological outcome. Conclusions Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.

Název v anglickém jazyce

Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders

Popis výsledku anglicky

Background Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation. Aims Determining the effect of diagnostic and therapeutic interventions on the neurological outcome. Methods Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry. Results About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 mu mol/L) best predicted the neurological outcome. Conclusions Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FB - Endokrinologie, diabetologie, metabolismus, výživa

OECD FORD obor

—

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Inherited Metabolic Disease

ISSN

0141-8955

e-ISSN

—

Svazek periodika

39

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

661-672

Kód UT WoS článku

000381986400006

EID výsledku v databázi Scopus

2-s2.0-84964308487