LAUSR

Introduction: Guanidinoacetate methyltransferase (GAMT) deficiency, also known as cerebral creatine deficiency syndrome type 2 (CCDS2), is an uncommon disease caused by an innate genetic defect in the metabolic pathway of creatine inherited in an autosomal recessive manner. It is a rare cause of neurological regression and epilepsy. In this report, we present the first GAMT deficiency case in Syria related to a novel variant. Case Presentation: A 2.5-year-old boy presented to the paediatric neurology clinic with evidence of neurodevelopmental delays and intellectual disabilities. Recurrent eye blinking, generalized non-motor (absence) seizures, hyperactivity, and poor eye contact were revealed in the neurological examination. Some athetoid and dystonic movements were noticed. His electroencephalography (EEG) was very disturbed because of generalized spike-wave and slow-wave discharges. Based on these findings antiepileptic drugs were administered. His seizures slightly improved, but then relapsed with myoclonic and drop attacks. After 6 years of unbeneficial treatment, a genetic test was required. Whole-exome sequencing was conducted and identified a novel homozygous GAMT variant (NM_138924.2:c.391+5G>C). Treatment with oral creatine supplementation, ornithine, and sodium benzoate was administered. After 1.7 years of follow-up, the child was almost seizure-free with a remarkable reduction of epileptic activity on EEG. He demonstrated good—but not complete—behavioural and motor improvement due to delayed diagnosis and treatment. Conclusion: GAMT deficiency should be considered in differential diagnoses in children with neurodevelopmental regression along with drug-refractory epilepsy. A special concern is needed in Syria for such genetic disorders; regarding the high prevalence of consanguinity. Whole-exome sequencing and genetic analysis can be used to diagnose this disorder. We reported a novel GAMT variant to extend its mutation spectrum and provide an additional molecular marker for the definitive diagnosis of GAMT deficiency patients and prenatal diagnosis in the affected families.