Electro-clinical features and long-term outcomes in guanidinoacetate methyltransferase (GAMT) deficiency


YILDIZ Y., Ardıçlı D., GÖÇMEN R., YALNIZOĞLU D., Topçu M., Coşkun T., ...More

European Journal of Paediatric Neurology, vol.49, pp.66-72, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 49
  • Publication Date: 2024
  • Doi Number: 10.1016/j.ejpn.2024.02.006
  • Journal Name: European Journal of Paediatric Neurology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Page Numbers: pp.66-72
  • Keywords: Cerebral creatine deficiency, Electroencephalogram (EEG), Epilepsy, Guanidinoacetate methyltransferase (GAMT) deficiency, Seizure
  • Hacettepe University Affiliated: Yes

Abstract

Objective: To evaluate clinical characteristics and long-term outcomes in patients with guanidinoacetate methyltransferase (GAMT) deficiency with a special emphasis on seizures and electroencephalography (EEG) findings. Methods: We retrospectively analyzed the clinical and molecular characteristics, seizure types, EEG findings, neuroimaging features, clinical severity scores, and treatment outcomes in six patients diagnosed with GAMT deficiency. Results: Median age at presentation and diagnosis were 11.5 months (8–12 months) and 63 months (18 months −11 years), respectively. Median duration of follow-up was 14 years. Global developmental delay (6/6) and seizures (5/6) were the most common symptoms. Four patients presented with febrile seizures. The age at seizure-onset ranged between 8 months and 4 years. Most common seizure types were generalized tonic seizures (n = 4) and motor seizures resulting in drop attacks (n = 3). Slow background activity (n = 5) and generalized irregular sharp and slow waves (n = 3) were the most common EEG findings. Burst-suppression and electrical status epilepticus during slow-wave sleep (ESES) pattern was present in one patient. Three of six patients had drug-resistant epilepsy. Post-treatment clinical severity scores showed improvement regarding movement disorders and epilepsy. All patients were seizure-free in the follow-up. Conclusions: Epilepsy is one of the main symptoms in GAMT deficiency with various seizure types and non-specific EEG findings. Early diagnosis and initiation of treatment are crucial for better seizure and cognitive outcomes. This long-term follow up study highlights to include cerebral creatine deficiency syndromes in the differential diagnosis of patients with global developmental delay and epilepsy and describes the course under treatment.