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.
| Original language | English |
|---|---|
| Title of host publication | JIMD Reports |
| Publisher | Springer |
| Pages | 65-69 |
| Number of pages | 5 |
| DOIs | |
| Publication status | Published - Jan 1 2014 |
Publication series
| Name | JIMD Reports |
|---|---|
| Volume | 12 |
| ISSN (Print) | 2192-8304 |
| ISSN (Electronic) | 2192-8312 |
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Keywords
- Creatine supplementation
- Creatine synthesis
- Intellectual disability
- Involuntary movement
- Splice site mutation
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cite this
A Japanese adult case of guanidinoacetate methyltransferase deficiency. / Akiyama, Tomoyuki; Osaka, Hitoshi; Shimbo, Hiroko; Nakajiri, Tomoshi; Kobayashi, Katsuhiro; Oka, Makio; Endoh, Fumika; Yoshinaga, Harumi.
JIMD Reports. Springer, 2014. p. 65-69 (JIMD Reports; Vol. 12).Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - A Japanese adult case of guanidinoacetate methyltransferase deficiency
AU - Akiyama, Tomoyuki
AU - Osaka, Hitoshi
AU - Shimbo, Hiroko
AU - Nakajiri, Tomoshi
AU - Kobayashi, Katsuhiro
AU - Oka, Makio
AU - Endoh, Fumika
AU - Yoshinaga, Harumi
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Creatine supplementation
KW - Creatine synthesis
KW - Intellectual disability
KW - Involuntary movement
KW - Splice site mutation
UR - http://www.scopus.com/inward/record.url?scp=84896137037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896137037&partnerID=8YFLogxK
U2 - 10.1007/8904_2013_245
DO - 10.1007/8904_2013_245
M3 - Chapter
AN - SCOPUS:84896137037
T3 - JIMD Reports
SP - 65
EP - 69
BT - JIMD Reports
PB - Springer
ER -