Objectives GM2 gangliosidosis is a rare form of inborn errors of metabolism including Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency. GM2 activator protein deficiency is an ultra-rare form of GM2 gangliosidosis. To date, 16 cases of GM2 activator protein deficiency have been reported in the literature, and among them, 11 cases were the infantile form of the disease. Here we report the first two patients from Turkey with the infantile form of the disease with a novel likely pathogenic variant. Case presentation A boy of eight months old presented to the metabolic department with very mild neurological deterioration, although he had achieved early developmental milestones at the appropriate time. The parents also had a daughter who had lost skills progressively before one year of age. The boy was evaluated and bilateral cherry-red spots were found with no abnormality in either metabolic screening including β-hexosaminidase or cranial magnetic resonance imaging. A novel homozygous likely pathogenic variant in GM2A was detected in a next-generation sequence panel revealing GM2 activator protein deficiency. His sister was investigated after he was diagnosed with GM2 activator deficiency and it was found that she had the same variant as her brother. Conclusions This case report emphasizes that in the event of normal β-hexosaminidase activity, GM2 activator protein deficiency could be underdiagnosed, and further molecular analysis should be performed. To the best of our knowledge, this boy is one of the youngest patient diagnosed with very mild symptoms. With this novel pathogenic variant, these patients have expanded the mutation spectrum of GM2 activator protein deficiency.

中文翻译：

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来自土耳其的两名 GM2A 基因新变异患者及文献复习

目的 GM2 神经节苷脂贮积症是一种罕见的先天性代谢障碍，包括 Tay-Sachs 病、Sandhoff 病和 GM2 激活剂缺乏症。GM2 激活蛋白缺乏症是一种极其罕见的 GM2 神经节苷脂沉积症。迄今为止，文献报道了 16 例 GM2 激活蛋白缺乏症，其中 11 例为婴儿型。在这里，我们报告了来自土耳其的前两名患有婴儿型疾病的患者，该患者具有一种新的可能的致病变异。病例介绍 一名八个月大的男孩因非常轻微的神经功能恶化就诊于代谢科，尽管他在适当的时间取得了早期发育里程碑。父母还有一个女儿，她在一岁前就逐渐丧失了技能。对该男孩进行了评估，发现双侧樱桃红色斑点，包括 β-氨基己糖苷酶在内的代谢筛查或颅脑磁共振成像均未见异常。在下一代序列面板中检测到 GM2A 中一种新的纯合可能致病变异，揭示了 GM2 激活蛋白缺乏症。在他被诊断出患有 GM2 激活剂缺乏症后，他的妹妹接受了调查，发现她和她的兄弟有相同的变异。结论 本病例报告强调，在β-氨基己糖苷酶活性正常的情况下，GM2激活蛋白缺乏可能被漏诊，应进行进一步的分子分析。据我们所知，这个男孩是被诊断出症状非常轻微的最年轻的患者之一。有了这个新的致病变异，