5‐Amino‐4‐imidazolecarboxamide‐ribosiduria (AICA)‐ribosiduria is an exceedingly rare autosomal recessive condition resulting from the disruption of the bifunctional purine biosynthesis protein PURH (ATIC), which catalyzes the last two steps of de novo purine synthesis. It is characterized biochemically by the accumulation of AICA‐riboside in urine. AICA‐ribosiduria had been reported in only one individual, 15 years ago. In this article, we report three novel cases of AICA‐ribosiduria from two independent families, with two novel pathogenic variants in ATIC. We also provide a clinical update on the first patient. Based on the phenotypic features shared by these four patients, we define AICA‐ribosiduria as the syndromic association of severe‐to‐profound global neurodevelopmental impairment, severe visual impairment due to chorioretinal atrophy, ante‐postnatal growth impairment, and severe scoliosis. Dysmorphic features were observed in all four cases, especially neonatal/infancy coarse facies with upturned nose. Early‐onset epilepsy is frequent and can be pharmacoresistant. Less frequently observed features are aortic coarctation, chronic hepatic cytolysis, minor genital malformations, and nephrocalcinosis. Alteration of the transformylase activity of ATIC might result in a more severe impairment than the alteration of the cyclohydrolase activity. Data from literature points toward a cytotoxic mechanism of the accumulated AICA‐riboside.

中文翻译：

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由于 ATIC 缺陷导致的 AICA-核糖尿症：三个新病例的表型描述，以及第一个病例的长期更新。

5-氨基-4-咪唑甲酰胺-核糖尿（AICA）-核糖尿是一种极为罕见的常染色体隐性遗传病，由双功能嘌呤生物合成蛋白PURH（ATIC）破坏引起，该蛋白催化嘌呤从头合成的最后两步。它的生化特征是 AICA-核糖苷在尿液中的积累。15 年前，AICA-ribosiduria 仅在一个个体中报告过。在这篇文章中，我们报告了来自两个独立家族的三例 AICA-核糖尿症的新病例，在ATIC 中有两个新的致病变异. 我们还提供了第一位患者的临床更新。基于这四名患者共有的表型特征，我们将 AICA-核糖尿症定义为严重至严重的整体神经发育障碍、脉络膜视网膜萎缩导致的严重视力障碍、产前生长障碍和严重脊柱侧弯的综合征关联。在所有四个病例中都观察到畸形特征，尤其是新生儿/婴儿期粗糙的面部，鼻子上翘。早发性癫痫很常见，并且可能具有耐药性。不太常见的特征是主动脉缩窄、慢性肝细胞溶解、轻微的生殖器畸形和肾钙质沉着症。ATIC 转化酶活性的改变可能导致比环化水解酶活性改变更严重的损害。