Alhomsi Dima, Abdalsalam Dania, Sulaiman Rama, Bakleh Sameer, Alasmar Diana
Faculty of Medicine, Damascus University.
Department of Neurology, Pediatrics University Hospital.
Ann Med Surg (Lond). 2023 Apr 11;85(5):1906-1910. doi: 10.1097/MS9.0000000000000385. eCollection 2023 May.
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.
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.
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.
胍乙酸甲基转移酶(GAMT)缺乏症,也称为2型脑肌酸缺乏综合征(CCDS2),是一种由肌酸代谢途径中的先天性遗传缺陷引起的罕见疾病,以常染色体隐性方式遗传。它是神经功能退化和癫痫的罕见病因。在本报告中,我们介绍了叙利亚首例与新变异相关的GAMT缺乏症病例。
一名2.5岁男孩因神经发育迟缓及智力残疾症状前往儿科神经科门诊就诊。神经检查发现反复眨眼、全身性非运动性(失神)发作、多动以及眼神交流不佳。还注意到一些手足徐动和张力障碍性动作。其脑电图(EEG)因广泛性棘波 - 慢波放电而严重紊乱。基于这些发现给予了抗癫痫药物治疗。他的癫痫发作稍有改善,但随后又复发并伴有肌阵挛和跌倒发作。经过6年无效治疗后,需要进行基因检测。进行了全外显子组测序,鉴定出一种新的纯合GAMT变异(NM_138924.2:c.391+5G>C)。给予口服补充肌酸、鸟氨酸和苯甲酸钠治疗。经过1.7年的随访,该患儿几乎无癫痫发作,脑电图上的癫痫活动显著减少。由于诊断和治疗延迟,他在行为和运动方面有了良好但未完全恢复的改善。
对于伴有药物难治性癫痫的神经发育退化儿童,鉴别诊断时应考虑GAMT缺乏症。在叙利亚,由于近亲结婚率高,对于此类遗传疾病需要特别关注。全外显子组测序和基因分析可用于诊断该疾病。我们报告了一种新的GAMT变异,以扩展其突变谱,并为GAMT缺乏症患者的确诊和受累家庭的产前诊断提供额外的分子标记。