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Early prediction of phenotypic severity in Citrullinemia Type 1

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Harvard

Zielonka, M, Kölker, S, Gleich, F, Stützenberger, N, Nagamani, SCS, Gropman, AL, Hoffmann, GF, Garbade, SF, Posset, R, Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group & Lund, AM 2019, 'Early prediction of phenotypic severity in Citrullinemia Type 1' Annals of Clinical and Translational Neurology, vol. 6, no. 9, pp. 1858-1871. https://doi.org/10.1002/acn3.50886

APA

Zielonka, M., Kölker, S., Gleich, F., Stützenberger, N., Nagamani, S. C. S., Gropman, A. L., ... Lund, A. M. (2019). Early prediction of phenotypic severity in Citrullinemia Type 1. Annals of Clinical and Translational Neurology, 6(9), 1858-1871. https://doi.org/10.1002/acn3.50886

CBE

Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL, Hoffmann GF, Garbade SF, Posset R, Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group, Lund AM. 2019. Early prediction of phenotypic severity in Citrullinemia Type 1. Annals of Clinical and Translational Neurology. 6(9):1858-1871. https://doi.org/10.1002/acn3.50886

MLA

Vancouver

Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL et al. Early prediction of phenotypic severity in Citrullinemia Type 1. Annals of Clinical and Translational Neurology. 2019;6(9):1858-1871. https://doi.org/10.1002/acn3.50886

Author

Zielonka, Matthias ; Kölker, Stefan ; Gleich, Florian ; Stützenberger, Nicolas ; Nagamani, Sandesh C S ; Gropman, Andrea L ; Hoffmann, Georg F ; Garbade, Sven F ; Posset, Roland ; Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group ; Lund, Allan Meldgaard. / Early prediction of phenotypic severity in Citrullinemia Type 1. In: Annals of Clinical and Translational Neurology. 2019 ; Vol. 6, No. 9. pp. 1858-1871.

Bibtex

@article{59efc55de580402eb720333a3870f9ba,
title = "Early prediction of phenotypic severity in Citrullinemia Type 1",
abstract = "OBJECTIVE: Citrullinemia type 1 (CTLN1) is an inherited metabolic disease affecting the brain which is detectable by newborn screening. The clinical spectrum is highly variable including individuals with lethal hyperammonemic encephalopathy in the newborn period and individuals with a mild-to-moderate or asymptomatic disease course. Since the phenotypic severity has not been predictable early during the disease course so far, we aimed to design a reliable disease prediction model.METHODS: We used a newly established mammalian biallelic expression system to determine residual enzymatic activity of argininosuccinate synthetase 1 (ASS1; OMIM #215700) in 71 individuals with CTLN1, representing 48 ASS1 gene variants and 50 different, mostly compound heterozygous combinations in total. Residual enzymatic ASS1 activity was correlated to standardized biochemical and clinical endpoints available from the UCDC and E-IMD databases.RESULTS: Residual enzymatic ASS1 activity correlates with peak plasma ammonium and L-citrulline concentrations at initial presentation. Individuals with 8{\%} of residual enzymatic ASS1 activity or less had more frequent and more severe hyperammonemic events and lower cognitive function than those above 8{\%}, highlighting that residual enzymatic ASS1 activity allows reliable severity prediction. Noteworthy, empiric clinical practice of affected individuals is in line with the predicted disease severity supporting the notion of a risk stratification-based guidance of therapeutic decision-making based on residual enzymatic ASS1 activity in the future.INTERPRETATION: Residual enzymatic ASS1 activity reliably predicts the phenotypic severity in CTLN1. We propose a new severity-adjusted classification system for individuals with CTLN1 based on the activity results of the newly established biallelic expression system.",
author = "Matthias Zielonka and Stefan K{\"o}lker and Florian Gleich and Nicolas St{\"u}tzenberger and Nagamani, {Sandesh C S} and Gropman, {Andrea L} and Hoffmann, {Georg F} and Garbade, {Sven F} and Roland Posset and {Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group} and Lund, {Allan Meldgaard}",
note = "{\circledC} 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.",
year = "2019",
doi = "10.1002/acn3.50886",
language = "English",
volume = "6",
pages = "1858--1871",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

RIS

TY - JOUR

T1 - Early prediction of phenotypic severity in Citrullinemia Type 1

AU - Zielonka, Matthias

AU - Kölker, Stefan

AU - Gleich, Florian

AU - Stützenberger, Nicolas

AU - Nagamani, Sandesh C S

AU - Gropman, Andrea L

AU - Hoffmann, Georg F

AU - Garbade, Sven F

AU - Posset, Roland

AU - Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group

A2 - Lund, Allan Meldgaard

N1 - © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

PY - 2019

Y1 - 2019

N2 - OBJECTIVE: Citrullinemia type 1 (CTLN1) is an inherited metabolic disease affecting the brain which is detectable by newborn screening. The clinical spectrum is highly variable including individuals with lethal hyperammonemic encephalopathy in the newborn period and individuals with a mild-to-moderate or asymptomatic disease course. Since the phenotypic severity has not been predictable early during the disease course so far, we aimed to design a reliable disease prediction model.METHODS: We used a newly established mammalian biallelic expression system to determine residual enzymatic activity of argininosuccinate synthetase 1 (ASS1; OMIM #215700) in 71 individuals with CTLN1, representing 48 ASS1 gene variants and 50 different, mostly compound heterozygous combinations in total. Residual enzymatic ASS1 activity was correlated to standardized biochemical and clinical endpoints available from the UCDC and E-IMD databases.RESULTS: Residual enzymatic ASS1 activity correlates with peak plasma ammonium and L-citrulline concentrations at initial presentation. Individuals with 8% of residual enzymatic ASS1 activity or less had more frequent and more severe hyperammonemic events and lower cognitive function than those above 8%, highlighting that residual enzymatic ASS1 activity allows reliable severity prediction. Noteworthy, empiric clinical practice of affected individuals is in line with the predicted disease severity supporting the notion of a risk stratification-based guidance of therapeutic decision-making based on residual enzymatic ASS1 activity in the future.INTERPRETATION: Residual enzymatic ASS1 activity reliably predicts the phenotypic severity in CTLN1. We propose a new severity-adjusted classification system for individuals with CTLN1 based on the activity results of the newly established biallelic expression system.

AB - OBJECTIVE: Citrullinemia type 1 (CTLN1) is an inherited metabolic disease affecting the brain which is detectable by newborn screening. The clinical spectrum is highly variable including individuals with lethal hyperammonemic encephalopathy in the newborn period and individuals with a mild-to-moderate or asymptomatic disease course. Since the phenotypic severity has not been predictable early during the disease course so far, we aimed to design a reliable disease prediction model.METHODS: We used a newly established mammalian biallelic expression system to determine residual enzymatic activity of argininosuccinate synthetase 1 (ASS1; OMIM #215700) in 71 individuals with CTLN1, representing 48 ASS1 gene variants and 50 different, mostly compound heterozygous combinations in total. Residual enzymatic ASS1 activity was correlated to standardized biochemical and clinical endpoints available from the UCDC and E-IMD databases.RESULTS: Residual enzymatic ASS1 activity correlates with peak plasma ammonium and L-citrulline concentrations at initial presentation. Individuals with 8% of residual enzymatic ASS1 activity or less had more frequent and more severe hyperammonemic events and lower cognitive function than those above 8%, highlighting that residual enzymatic ASS1 activity allows reliable severity prediction. Noteworthy, empiric clinical practice of affected individuals is in line with the predicted disease severity supporting the notion of a risk stratification-based guidance of therapeutic decision-making based on residual enzymatic ASS1 activity in the future.INTERPRETATION: Residual enzymatic ASS1 activity reliably predicts the phenotypic severity in CTLN1. We propose a new severity-adjusted classification system for individuals with CTLN1 based on the activity results of the newly established biallelic expression system.

U2 - 10.1002/acn3.50886

DO - 10.1002/acn3.50886

M3 - Journal article

VL - 6

SP - 1858

EP - 1871

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

SN - 2328-9503

IS - 9

ER -

ID: 58997425