Childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) is a recently described form of the large group of infantile hereditary lower motor neuron diseases (Teoh et al. 2017), resulting from biallelic damaging variants in the AGTPBP1 gene, first described by Shashi et al. in EMBO J 37(23):e100540, 2018. AGTPBP-related neurodegeneration is a severe neurodevelopmental disorder that progresses with global developmental delay and intellectual disability, often accompanied with peripheral nerve damage and lower motor degeneration and a fatal course in the early years of life. The encoded protein is ATP/GTP-Binding Protein1, also known as cytosolic carboxypeptidase 1 (CCP1) or nervous system nuclear protein induced by axotomy (NNA1). Here we report a consanguineous family with four offspring, two of whom are affected. The index patient is a 21-month-old male with global developmental delay and hypotonia. The proband’s 17-year-old sister, diagnosed with cerebral palsy, had severe hypotonia accompanied by motor and cognitive retardation. WES analysis revealed a novel homozygous c.3293G > A variant in the AGTPBP1 gene with high pathogenicity scores. Targeted Sanger sequencing confirmed the variant in both affected children and in heterozygous form in the parents. The affected siblings present with hypotonia and motor and cognitive retardation, in line with the studies previously reported. However, in our patients, no signs of cerebellar atrophy in cranial MRI were present, so the acronym CONDCA is not applicable; lower motor neuron findings were also absent. The matching and distinguishing aspects of our patients will add to the present literature and expand our understanding of this rare genetic neurodegenerative disease of early childhood.

伴有小脑萎缩的儿童期神经变性 (CONDCA) 是最近描述的一大类婴儿遗传性下运动神经元疾病的形式 (Teoh et al. 2017)，由AGTPBP1中的双等位基因破坏性变异引起基因，首先由 Shashi 等人 描述。在 EMBO J 37(23):e100540, 2018 中。AGTPBP 相关的神经变性是一种严重的神经发育障碍，随着全球发育迟缓和智力残疾而进展，通常伴有周围神经损伤和下运动变性，并在早期出现致命的病程。生活。编码的蛋白质是 ATP/GTP 结合蛋白 1，也称为细胞溶质羧肽酶 1 (CCP1) 或轴切术诱导的神经系统核蛋白 (NNA1)。在这里，我们报告了一个有四个后代的近亲家庭，其中两个受到影响。指示患者是一名 21 个月大的男性，患有整体发育迟缓和肌张力减退。先证者 17 岁的妹妹被诊断患有脑瘫，患有严重的肌张力减退并伴有运动和认知迟缓。WES分析揭示了一种新的纯合c。AGTPBP1基因具有高致病性评分。靶向 Sanger 测序证实了受影响儿童和父母中杂合形式的变异。与先前报道的研究一致，受影响的兄弟姐妹出现肌张力减退以及运动和认知迟缓。然而，在我们的患者中，头颅 MRI 中没有小脑萎缩的迹象，因此首字母缩略词 CONDCA 不适用；也没有下运动神经元的发现。我们患者的匹配和区分方面将增加现有文献，并扩大我们对这种罕见的儿童早期遗传神经退行性疾病的理解。