Wyeliminowanie opornej na leki epilepsji u dorosłej pacjentki z niedoborem GAMT: Opis przypadku i przegląd piśmiennictwa

OBJECTIVE: Guanidinoacetate methyltransferase (GAMT) deficiency is a rare autosomal recessive creatine biosynthesis disorder. Reports specifically focusing on adult patients remain scarce. METHODS: We report a 52-year-old female (the oldest documented case of GAMT deficiency to date) presenting with severe intellectual disability, refractory epilepsy, and adult-onset disease progression. Whole-exome sequencing identified novel compound heterozygous GAMT variants (c.265_267del and c.253G>T), and magnetic resonance spectroscopy confirmed cerebral creatine depletion. Remarkably, initiating oral creatine supplementation at age 52 achieved complete seizure freedom, normalization of the electroencephalogram (EEG), and significant motor function recovery. RESULTS: A comprehensive review revealed that untreated adult patients face a high risk of progressive neurological deterioration. Compared to the pediatric cohort, adults exhibited a significantly higher prevalence of movement disorders (69.2% vs. 33.1%, p < 0.001) and a trend toward a higher prevalence of epilepsy (92.3% vs. 74.2%). Especially, atonic seizures (drop attacks) are particularly characteristic of adult GAMT deficiency, with EEGs frequently demonstrating background slowing, multifocal epileptiform discharges, and electrodecremental patterns. SIGNIFICANCE: This study underscores that continuous disease progression and prolonged neurotoxicity still could compromise the well-being of adult GAMT deficiency patients. Accurate diagnosis is essential for adults presenting with developmental and epileptic encephalopathy (DEE) phenotype, as even late treatment for GAMT deficiency can still dramatically alleviate the epileptic burden and reverse motor decline. PLAIN LANGUAGE SUMMARY: We report the oldest known adult diagnosed with GAMT deficiency. Our case demonstrates that starting creatine treatment even at age 52 can dramatically reduce seizures and restore motor function. Literature shows that untreated adults suffer from more severe epilepsy and movement disorders than children, with symptoms worsening over time. These findings highlight the critical need for genetic testing in adults with unexplained severe epilepsy; timely creatine supplementation can halt cognitive decline and significantly restore quality of life.