ALG13-CDG with Infantile Spasms in a Male Patient Due to a De Novo ALG13 Gene Mutation
ALG13-CDG with Infantile Spasms in a Male Patient Due to a De Novo ALG13 Gene Mutation
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DOI：
10.1007/8904_2017_53
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发表时间：
2018-01-01
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影响因子：
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通讯作者：
Verrips, Aad
中科院分区：
文献类型：
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作者：
Galama, Wienke H.;Verhaagen-van den Akker, Sandra L. J.;Verrips, Aad
一名男婴在3.5个月大时出现发育迟缓。1个月后，他出现婴儿痉挛，脑电检查显示心律失常。其他症状包括视觉发育延迟、不对称性听力损失、低眼压和编舞运动。他也有一些畸形特征，很容易受到感染。他先后接受了维甲菊酯、强的松龙、丙戊酸、硝西潘和拉莫三嗪的治疗，但没有持久的临床效果，但对左乙拉西坦有治疗反应。脑部核磁共振检查显示胼胝体发育不良，髓鞘形成轻度延迟。进一步的检查，包括代谢筛选和转铁蛋白等电聚焦的糖基化研究，都被认为是正常的。全外显子组测序发现ALG13基因存在从头突变(C.320A>；G，p.Asn107Ser)。该基因突变位于X染色体上，与先天性I型糖基化障碍(CDG-I)有关。转铁蛋白的质谱分析显示轻微的糖基化异常。到目前为止，ALG13中的c.320A和gt；G突变只在女孩中被描述，并被认为对男孩是致命的。所有带有这种特殊突变的女孩都表现出类似的发育迟缓和严重的早发性癫痫的表型。对两名女孩进行了糖基化研究，结果显示糖基化模式正常。这是第一个出现由ALG13基因c.320A>；G突变引起的癫痫脑病的男孩。由于这种突变患者的糖基化研究接近正常，如果不进行遗传学研究，可能会错过ALG13-CDG的诊断。
A boy presented at the age of 3.5 months with a developmental delay. He developed infantile spasms with hypsarrhytmia on EEG 1 month later. Additional symptoms were delayed visual development, asymmetrical hearing loss, hypotonia, and choreoathetoid movements. He also had some dysmorphic features and was vulnerable for infections. He was treated successively with vigabatrin, prednisolone, valproic acid, nitrazepam, and lamotrigine without a lasting clinical effect, but showed a treatment response to levetiracetam. Cerebral MRI showed hypoplasia of the corpus callosum and a mild delay in myelination. Further investigations including metabolic screening and glycosylation studies by transferrin isoelectric focusing were all considered to be normal. Whole-exome sequencing identified a de novo mutation in the ALG13 gene (c.320A>G, p.(Asn107Ser)). Mutations in this gene, which is located on the X-chromosome, are associated with congenital disorders of glycosylation type I (CDG-I). Mass spectrometric analysis of transferrin showed minor glycosylation abnormalities. The c.320A>G mutation in ALG13 has until now only been described in girls and was thought to be lethal for boys. All girls with this specific mutation presented with a similar phenotype of developmental delay and severe early onset epilepsy. In two girls glycosylation studies were performed which showed a normal glycosylation pattern. This is the first boy presenting with an onepileptic encephalopathy caused by the c.320A>G mutation in the ALG13 gene. Since glycosylation studies are near-normal in patients with this mutation, the diagnosis of ALG13-CDG can be missed if genetic studies are not performed.