Papers

Peer-reviewed International journal
2014

A Japanese adult case of guanidinoacetate methyltransferase deficiency.

JIMD reports
  • Akiyama T
  • ,
  • Osaka H
  • ,
  • Shimbo H
  • ,
  • Nakajiri T
  • ,
  • Kobayashi K
  • ,
  • Oka M
  • ,
  • Endoh F
  • ,
  • Yoshinaga H

Volume
12
Number
First page
65
Last page
69
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1007/8904_2013_245

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.

Link information
DOI
https://doi.org/10.1007/8904_2013_245
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23846910
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897789
ID information
  • DOI : 10.1007/8904_2013_245
  • ISSN : 2192-8304
  • Pubmed ID : 23846910
  • Pubmed Central ID : PMC3897789

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