Service de Neurologie and Laboratoire de Neurosciences, CHU Mustapha Bacha, Université d'Alger, Algeria.
Neuromuscul Disord. 2013 Aug;23(8):670-4. doi: 10.1016/j.nmd.2013.04.011. Epub 2013 Jun 14.
We report two sisters, aged 11 and 6years, with AGAT deficiency syndrome (OMIM 612718) which is the least common creatine deficiency syndrome. They were born full-term to consanguineous parents and had moderate developmental delay. Examination showed an important language delay, a progressive proximal muscular weakness in the lower limbs with Gowers sign and myopathic electromyography. Investigations revealed undetectable guanidinoacetate and low level of creatine in plasma and urine, characteristic findings of AGAT deficiency syndrome. Brain magnetic resonance spectroscopy showed a markedly reduced level of creatine. Guanidinoacetate methyltransferase (GATM) gene sequencing revealed a homozygous missense mutation in exon 4:c.608A>C, (p.Tyr203Ser). Thirteen months after beginning the treatment with oral creatine monohydrate 200mg/kg/day, then 400mg/kg/day, there was a dramatic improvement in muscle strength with Gowers sign disappearance in both patients, and a mild improvement in language and cognitive functions. AGAT deficiency syndrome should be considered in all patients with language retardation and cognitive impairment associated to a myopathy of unknown etiology such that early diagnosis must lead to creatine supplementation to cure the myopathy and improve language and cognitive function.
我们报告了两例患有 AGAT 缺乏症（OMIM 612718）的姐妹，年龄分别为 11 岁和 6 岁，这是最不常见的肌酸缺乏症之一。她们均足月出生于近亲父母，存在中度发育迟缓。检查发现存在明显的语言发育迟缓、进行性下肢近端肌肉无力伴 Gowers 征和肌病性肌电图。检查结果显示血液和尿液中胍基乙酸盐无法检测到，肌酸水平低，这是 AGAT 缺乏症的特征性发现。大脑磁共振波谱显示肌酸水平明显降低。胍基乙酸甲基转移酶（GATM）基因测序显示第 4 外显子中存在纯合错义突变：c.608A>C，（p.Tyr203Ser）。开始每天口服肌酸一水合物 200mg/kg，然后增加至 400mg/kg 治疗 13 个月后，两名患者的肌肉力量均有显著改善，Gowers 征消失，语言和认知功能也有轻度改善。如果存在病因不明的肌病并伴有语言发育迟缓和认知障碍，应考虑 AGAT 缺乏症，因此早期诊断必须进行肌酸补充以治疗肌病并改善语言和认知功能。
