Guanidinoacetate methyltransferase deficiency: a rare but treatable cause of developmental and epileptic encephalopathy – a case report and literature review
Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland
Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland
Pediatr Endocrinol Diabetes Metab 2026; 32 (4):
Guanidinoacetate N-methyltransferase (GAMT) deficiency is a rare autosomal recessive cerebral creatine deficiency syndrome characterized by neurotoxic guanidinoacetate accumulation, creatine depletion, and developmental and epileptic encephalopathy. A seven-year-old girl with global developmental delay, autistic features, and drug-resistant epilepsy was diagnosed with a novel homozygous GAMT variant, c.520T>C (p.Trp174Arg), confirmed by next-generation sequencing and supported by the absence of the brain creatine peak on magnetic resonance spectroscopy. Targeted treatment with high-dose creatine monohydrate, ornithine, sodium benzoate, and arginine restriction resulted in rapid and sustained seizure freedom and marked improvement in cognition, speech, and adaptive skills during more than five years of follow-up. This case underlines the importance of early recognition of GAMT deficiency and comprehensive metabolic therapy, and supports the inclusion of GAMT deficiency in newborn screening programs.
Keywords
inborn errors of metabolism, GAMT deficiency, cerebral creatine deficiency syndromes, developmental and epileptic encephalopathy
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