Short Report

Journal of Inherited Metabolic Disease

, Volume 30, Issue 1, pp 100-100

Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy

  • A. A. M. MorrisAffiliated withWillink Unit, Royal Manchester Children’s Hospital Email author 
  • , R. E. AppletonAffiliated withDepartment of Neurology, Royal Liverpool Children’s Hospital
  • , B. PowerAffiliated withDepartment of Neurology, Royal Liverpool Children’s Hospital
  • , D. M. IsherwoodAffiliated withDepartment of Biochemistry, Royal Liverpool Children’s Hospital
  • , L. J. AbernethyAffiliated withDepartment of Radiology, Royal Liverpool Children’s Hospital
  • , R. W. TaylorAffiliated withMitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne
  • , D. M. TurnbullAffiliated withMitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne
  • , N. M. VerhoevenAffiliated withDepartment of Clinical Chemistry, Metabolic Unit, VU University Medical Center
  • , G. S. SalomonsAffiliated withDepartment of Clinical Chemistry, Metabolic Unit, VU University Medical Center
    • , C. JakobsAffiliated withDepartment of Clinical Chemistry, Metabolic Unit, VU University Medical Center

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Summary

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis. We report a patient who presented at 10 months of age with hypotonia and global developmental delay. Subsequently, she developed seizures and choreoathetosis. Magnetic resonance imaging showed high signal bilaterally in the globus pallidus on T2-weighted images. Mitochondrial respiratory chain studies revealed low complex I activity (in muscle 0.052 nmol NADH oxidized per min per unit citrate synthase, controls 0.166 ± 0.047; in fibroblasts 0.080 nmol NADH oxidized per min per unit citrate synthase, controls 0.197 ± 0.034). The true diagnosis was suspected at 21 months of age because of persistent low plasma and urine creatinine concentrations. GAMT activity was undetectable in fibroblasts and compound heterozygous mutations were found in the GAMT gene (c.327G>A and c.522G>A). The patient was treated with creatine, dietary arginine restriction and ornithine supplements. Her movement disorder and seizures resolved but she still has severe cognitive impairment and no expressive language. The occurrence of secondary respiratory chain abnormalities in GAMT deficiency may lead to misdiagnosis, particularly as the clinical and radiological features resemble those seen in mitochondrial encephalopathies. It is important to establish the correct diagnosis because specific treatment is available.