Abstract
Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis resulting in cerebral creatine depletion. We present a 38-year-old patient, the first Japanese case of GAMT deficiency. Developmental delay started after a few months of age with a marked delay in language, which resulted in severe intellectual deficit. She showed hyperactivity and trichotillomania from childhood. Epileptic seizures appeared at 18 months and she had multiple types of seizures including epileptic spasms, brief tonic seizures, atypical absences, complex partial seizures with secondary generalization, and “drop” seizures. They have been refractory to multiple antiepileptic drugs. Although there have been no involuntary movements, magnetic resonance imaging revealed T2 hyperintense lesions in bilateral globus pallidi. Motor regression started around 30 years of age and the patient is now able to walk for only short periods. Very low serum creatinine levels measured by enzymatic method raised a suspicion of GAMT deficiency, which was confirmed by proton magnetic resonance spectroscopy and urinary guanidinoacetate assay. GAMT gene analysis revealed that the patient is a compound heterozygote of c.578A>G, p.Gln193Arg and splice site mutation, c.391G>C, p.Gly131Arg, neither of which have been reported in the literature. We also identified two aberrant splice products from the patient’s cDNA analysis. The patient was recently started on supplementation of high-dose creatine and ornithine, the effects of which are currently under evaluation. Although rare, patients with developmental delay, epilepsy, behavioral problems, and movement disorders should be vigorously screened for GAMT deficiency, as it is a treatable disorder.
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Communicated by: Cornelis Jakobs, PhD Competing interests: None declared
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A 38-year-old patient, the first Japanese case of guanidinoacetate methyltransferase deficiency with two novel gene mutations (splice site mutation and missense mutation) was reported.
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Tomoyuki Akiyama, Hitoshi Osaka, Hiroko Shimbo, and Tomoshi Nakajiri: Drafting/revising the manuscript for content, analysis, and interpretation of data
Katsuhiro Kobayashi, Makio Oka, Fumika Endoh, and Harumi Yoshinaga: Drafting/revising the manuscript for content
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Tomoyuki Akiyama
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This study was approved by the ethics board at Kanagawa Children’s Medical Center.
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Tomoyuki Akiyama, Hitoshi Osaka, Hiroko Shimbo, Tomoshi Nakajiri, Katsuhiro Kobayashi, Makio Oka, Fumika Endoh, and Harumi Yoshinaga declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
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Akiyama, T. et al. (2013). A Japanese Adult Case of Guanidinoacetate Methyltransferase Deficiency. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 12. JIMD Reports, vol 12. Springer, Cham. https://doi.org/10.1007/8904_2013_245
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DOI: https://doi.org/10.1007/8904_2013_245
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