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Ann Clin Lab Sci. 2016 Sep;46(5):557-61.

Creatine Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures, and Behavioral Changes, but Normal Structural MRI.

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Department of Pediatrics and Medical Genetics, Medical University - Plovdiv, Sofia, Bulgaria
Department of Pediatrics and Medical Genetics, Medical University - Plovdiv, Sofia, Bulgaria.
Department of Imaging Diagnosis, University Hospital "St. Ivan Rilski" Sofia, Sofia, Bulgaria.
Molecular Neurogenomics Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerpen, Holland; Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University-Sofia, Sofia, Bulgaria.
National Genetic Laboratory, University Hospital of Obstetrics and Gynecology, Sofia; Department of Analytical Chemistry, Sofia University "St. Kl. Ohridsky", Sofia, Bulgaria.


A case with GAMT deficiency (homozygous c.64dupG mutation) presented with neurodevelopmental delay, rare seizures, behavioral disturbances, and mild hypotonia, posing diagnostic challenges. Metabolic investigations showed low creatinine in plasma and urine (guanidinoacetate couldn't be investigated) and slightly elevated lactate. MRI was normal. Correct diagnosis was possible only after MR spectroscopy was performed at age 5½ years. A homozygous c.64dupG mutation of the GAMT gene was identified in the proband. In conclusion, every case with neurodevelopmental delay or arrest, especially when accompanied by seizures, behavioral impairment, muscle hypotonia or extrapyramidal symptoms should undergo MRI with MR spectroscopy. Normal structural MRI doesn't exclude a creatine deficiency syndrome. Biochemical investigations of guanidinoacetate, creatine, and creatinine in body fluid should be done to diagnose cerebral creatine deficiency syndromes and to specify the deficient enzyme. Thus, a treatable disease will not be missed.


GAMT deficiency; MR spectroscopy; MRI; behavioral impairment; creatine deficiency; neurodevelopmental delay

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