TY - JOUR
T1 - Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: 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
PY - 2018
Y1 - 2018
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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042625062&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29506905
U2 - https://doi.org/10.1016/j.ejpn.2018.02.007
DO - https://doi.org/10.1016/j.ejpn.2018.02.007
M3 - Article
C2 - 29506905
SN - 1090-3798
VL - 22
SP - 369
EP - 379
JO - European Journal of Paediatric Neurology
JF - European Journal of Paediatric Neurology
IS - 3
ER -