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Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study

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Harvard

Khaikin, Y, Sidky, S, Abdenur, J, Anastasi, A, Ballhausen, D, Buoni, S, Chan, A, Cheillan, D, Dorison, N, Goldenberg, A, Goldstein, J, Hofstede, FC, Jacquemont, M-L, Koeberl, DD, Lion-Francois, L, Lund, AM, Mention, K, Mundy, H, O'Rourke, D, Pitelet, G, Raspall-Chaure, M, Tassini, M, Billette de Villemeur, T, Williams, M, Salomons, GS & Mercimek-Andrews, S 2018, 'Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study' European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, bind 22, nr. 3, s. 369-379. https://doi.org/10.1016/j.ejpn.2018.02.007

APA

CBE

Khaikin Y, Sidky S, Abdenur J, Anastasi A, Ballhausen D, Buoni S, Chan A, Cheillan D, Dorison N, Goldenberg A, Goldstein J, Hofstede FC, Jacquemont M-L, Koeberl DD, Lion-Francois L, Lund AM, Mention K, Mundy H, O'Rourke D, Pitelet G, Raspall-Chaure M, Tassini M, Billette de Villemeur T, Williams M, Salomons GS, Mercimek-Andrews S. 2018. Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 22(3):369-379. https://doi.org/10.1016/j.ejpn.2018.02.007

MLA

Vancouver

Author

Khaikin, Yannay ; Sidky, Sarah ; Abdenur, Jose ; Anastasi, Arnaud ; Ballhausen, Diana ; Buoni, Sabrina ; Chan, Alicia ; Cheillan, David ; Dorison, Nathalie ; Goldenberg, Alice ; Goldstein, Jennifer ; Hofstede, Floris C ; Jacquemont, Marie-Line ; Koeberl, Dwight D ; Lion-Francois, Laurence ; Lund, Allan Meldgaard ; Mention, Karine ; Mundy, Helen ; O'Rourke, Declan ; Pitelet, Gaele ; Raspall-Chaure, Miquel ; Tassini, Maria ; Billette de Villemeur, Thierry ; Williams, Monique ; Salomons, Gajja S ; Mercimek-Andrews, Saadet. / Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency : An international retrospective cohort study. I: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2018 ; Bind 22, Nr. 3. s. 369-379.

Bibtex

@article{563b8c09e53e4c3abb4efa9584515960,
title = "Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study",
abstract = "PURPOSE: Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder caused by pathogenic variants in GAMT. Brain creatine depletion and guanidinoacetate accumulation cause developmental delay, seizures and movement disorder. Treatment consists of creatine, ornithine and arginine-restricted diet. We initiated an international treatment registry using Research Electronic Data Capture (REDCap) software to evaluate treatment outcome.METHODS: Physicians completed an online REDCap questionnaire. Clinical severity score applied pre-treatment and on treatment.RESULTS: There were 22 patients. All had developmental delay, 18 had seizures and 8 had movement disorder. Based on the clinical severity score, 5 patients had a severe, 14 patients had a moderate and 3 patients had a mild phenotype. All patients had pathogenic variants in GAMT. The phenotype ranged from mild to moderate in patients with the most common c.327G > A variant. The phenotype ranged from mild to severe in patients with truncating variants. All patients were on creatine, 18 patients were on ornithine and 15 patients were on arginine- or protein-restricted diet. Clinical severity score improved in 13 patients on treatment. Developmental delay improved in five patients. One patient achieved normal development. Eleven patients became seizure free. Movement disorder resolved in four patients.CONCLUSION: In our small patient cohort, there seems to be no phenotype-genotype correlation. Creatine and ornithine and/or arginine- or protein-restricted diet were the most useful treatment to improve phenotype.",
keywords = "Cohort Studies, Creatine/administration & dosage, Diet, Protein-Restricted/methods, Female, Guanidinoacetate N-Methyltransferase/deficiency, Humans, Language Development Disorders/complications, Male, Movement Disorders/complications, Ornithine/administration & dosage, Retrospective Studies, Seizures/drug therapy, Treatment Outcome",
author = "Yannay Khaikin and Sarah Sidky and Jose Abdenur and Arnaud Anastasi and Diana Ballhausen and Sabrina Buoni and Alicia Chan and David Cheillan and Nathalie Dorison and Alice Goldenberg and Jennifer Goldstein and Hofstede, {Floris C} and Marie-Line Jacquemont and Koeberl, {Dwight D} and Laurence Lion-Francois and Lund, {Allan Meldgaard} and Karine Mention and Helen Mundy and Declan O'Rourke and Gaele Pitelet and Miquel Raspall-Chaure and Maria Tassini and {Billette de Villemeur}, Thierry and Monique Williams and Salomons, {Gajja S} and Saadet Mercimek-Andrews",
note = "Crown Copyright {\circledC} 2018. Published by Elsevier Ltd. All rights reserved.",
year = "2018",
month = "5",
doi = "10.1016/j.ejpn.2018.02.007",
language = "English",
volume = "22",
pages = "369--379",
journal = "European Journal of Paediatric Neurology",
issn = "1090-3798",
publisher = "W.B./Saunders Co. Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency

T2 - An international retrospective cohort study

AU - Khaikin, Yannay

AU - Sidky, Sarah

AU - Abdenur, Jose

AU - Anastasi, Arnaud

AU - Ballhausen, Diana

AU - Buoni, Sabrina

AU - Chan, Alicia

AU - Cheillan, David

AU - Dorison, Nathalie

AU - Goldenberg, Alice

AU - Goldstein, Jennifer

AU - Hofstede, Floris C

AU - Jacquemont, Marie-Line

AU - Koeberl, Dwight D

AU - Lion-Francois, Laurence

AU - Lund, Allan Meldgaard

AU - Mention, Karine

AU - Mundy, Helen

AU - O'Rourke, Declan

AU - Pitelet, Gaele

AU - Raspall-Chaure, Miquel

AU - Tassini, Maria

AU - Billette de Villemeur, Thierry

AU - Williams, Monique

AU - Salomons, Gajja S

AU - Mercimek-Andrews, Saadet

N1 - Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

PY - 2018/5

Y1 - 2018/5

N2 - PURPOSE: Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder caused by pathogenic variants in GAMT. Brain creatine depletion and guanidinoacetate accumulation cause developmental delay, seizures and movement disorder. Treatment consists of creatine, ornithine and arginine-restricted diet. We initiated an international treatment registry using Research Electronic Data Capture (REDCap) software to evaluate treatment outcome.METHODS: Physicians completed an online REDCap questionnaire. Clinical severity score applied pre-treatment and on treatment.RESULTS: There were 22 patients. All had developmental delay, 18 had seizures and 8 had movement disorder. Based on the clinical severity score, 5 patients had a severe, 14 patients had a moderate and 3 patients had a mild phenotype. All patients had pathogenic variants in GAMT. The phenotype ranged from mild to moderate in patients with the most common c.327G > A variant. The phenotype ranged from mild to severe in patients with truncating variants. All patients were on creatine, 18 patients were on ornithine and 15 patients were on arginine- or protein-restricted diet. Clinical severity score improved in 13 patients on treatment. Developmental delay improved in five patients. One patient achieved normal development. Eleven patients became seizure free. Movement disorder resolved in four patients.CONCLUSION: In our small patient cohort, there seems to be no phenotype-genotype correlation. Creatine and ornithine and/or arginine- or protein-restricted diet were the most useful treatment to improve phenotype.

AB - PURPOSE: Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder caused by pathogenic variants in GAMT. Brain creatine depletion and guanidinoacetate accumulation cause developmental delay, seizures and movement disorder. Treatment consists of creatine, ornithine and arginine-restricted diet. We initiated an international treatment registry using Research Electronic Data Capture (REDCap) software to evaluate treatment outcome.METHODS: Physicians completed an online REDCap questionnaire. Clinical severity score applied pre-treatment and on treatment.RESULTS: There were 22 patients. All had developmental delay, 18 had seizures and 8 had movement disorder. Based on the clinical severity score, 5 patients had a severe, 14 patients had a moderate and 3 patients had a mild phenotype. All patients had pathogenic variants in GAMT. The phenotype ranged from mild to moderate in patients with the most common c.327G > A variant. The phenotype ranged from mild to severe in patients with truncating variants. All patients were on creatine, 18 patients were on ornithine and 15 patients were on arginine- or protein-restricted diet. Clinical severity score improved in 13 patients on treatment. Developmental delay improved in five patients. One patient achieved normal development. Eleven patients became seizure free. Movement disorder resolved in four patients.CONCLUSION: In our small patient cohort, there seems to be no phenotype-genotype correlation. Creatine and ornithine and/or arginine- or protein-restricted diet were the most useful treatment to improve phenotype.

KW - Cohort Studies

KW - Creatine/administration & dosage

KW - Diet, Protein-Restricted/methods

KW - Female

KW - Guanidinoacetate N-Methyltransferase/deficiency

KW - Humans

KW - Language Development Disorders/complications

KW - Male

KW - Movement Disorders/complications

KW - Ornithine/administration & dosage

KW - Retrospective Studies

KW - Seizures/drug therapy

KW - Treatment Outcome

U2 - 10.1016/j.ejpn.2018.02.007

DO - 10.1016/j.ejpn.2018.02.007

M3 - Journal article

VL - 22

SP - 369

EP - 379

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

SN - 1090-3798

IS - 3

ER -

ID: 56311350