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

Autor: Alicia Chan, Gaele Pitelet, Sarah Sidky, Dwight D. Koeberl, Thierry Billette de Villemeur, K. Mention, Floris C. Hofstede, Declan O'Rourke, Laurence Lion-François, Gajja S. Salomons, Diana Ballhausen, Jose E. Abdenur, Marie-Line Jacquemont, Maria Tassini, David Cheillan, Nathalie Dorison, Miquel Raspall-Chaure, Monique Williams, Jennifer L. Goldstein, Alice Goldenberg, Arnaud Anastasi, Sabrina Buoni, Saadet Mercimek-Andrews, Helen Mundy, Allan M. Lund, Yannay Khaikin
Přispěvatelé: Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Pediatrics, Laboratory Medicine, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Reproduction & Development (AR&D)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Ornithine
medicine.medical_specialty
Movement disorders
Creatine therapy
Global developmental delay
Guanidinoacetate methyltransferase deficiency
Creatine
Cohort Studies
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Seizures
Internal medicine
medicine
Diet
Protein-Restricted
Humans
Language Development Disorders
Retrospective Studies
Movement Disorders
business.industry
Retrospective cohort study
General Medicine
medicine.disease
Seizure
Guanidinoacetate N-methyltransferase
030104 developmental biology
Treatment Outcome
chemistry
Pediatrics
Perinatology and Child Health
Female
Guanidinoacetate N-Methyltransferase
Neurology (clinical)
medicine.symptom
Arginine-restricted diet
business
030217 neurology & neurosurgery
GAMT deficiency
Cohort study
Zdroj: European journal of paediatric neurology : EJPN, 22(3), 369-379. W.B. Saunders Ltd
European Journal of Paediatric Neurology, 22(3), 369. W.B. Saunders Ltd
European Journal of Paediatric Neurology, 22(3), 369-379. W.B. Saunders
European Journal of Paediatric Neurology, 22(3), 369-379. W.B. Saunders Ltd
Khaikin, Y, Sidky, S, Abdenur, J, Anastasi, A, Ballhausen, D, Buoni, S, Chan, A, Cheillan, D, Dorison, N, Goldenberg, A, Goldstein, J, Hofstede, F C, Jacquemont, M-L, Koeberl, D D, Lion-Francois, L, Lund, A M, Mention, K, Mundy, H, O'Rourke, D, Pitelet, G, Raspall-Chaure, M, Tassini, M, Billette de Villemeur, T, Williams, M, Salomons, G S & Mercimek-Andrews, S 2018, ' Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study ', European Journal of Paediatric Neurology, vol. 22, no. 3, pp. 369-379 . https://doi.org/10.1016/j.ejpn.2018.02.007
ISSN: 1090-3798
DOI: 10.1016/j.ejpn.2018.02.007
Popis: 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.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.
Databáze: OpenAIRE
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