Guanidinoacetate methyltransferase deficiency, a treatable cause of intellectual disability in late childhood

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare, treatable creatine deficiency disorder presenting with intellectual disability, seizures, and behavioral issues. Early recognition and intervention can improve outcomes, but diagnosis is often delayed in a developing country like ours. A 15-year-old girl presented with developmental delay, predominantly affecting speech and social domains, and drug-resistant drop attacks since age five. She was diagnosed with an autism spectrum disorder with myoclonic-atonic seizures and provided supportive care in various hospitals prior. After a thorough evaluation, her biochemical tests showed low serum creatine and elevated guanidacetate levels. Magnetic resonance spectroscopy confirmed reduced creatine peaks. Whole exome sequencing identified a pathogenic homozygous variant in the GAMT gene. She was started on oral creatine monohydrate and L-ornithine alongside ongoing antiepileptic therapy. On follow-up, improvements were observed in cognition and social interaction, with reduced hyperactivity. GAMT deficiency, though rare, should be considered in children with unexplained developmental delays and seizures. Early diagnosis and treatment can prevent severe neurological impairment.