中国实用儿科杂志

中国实用儿科杂志 ›› 2024, Vol. 39 ›› Issue (10): 747-751.DOI: 10.19538/j.ek2024100607

• 专题笔谈 • 上一篇    下一篇

尿苷代谢异常与发育性癫痫性脑病50型的诊断与治疗

  

  1. 1.郑州大学附属儿童医院  河南省儿童医院  郑州儿童医院  a 河南省儿童神经发育工程研究中心，b 内分泌与遗传代谢科，河南  郑州  450018；2.北京大学第一医院儿童医学中心，北京  102600
  • 出版日期:2024-10-06 发布日期:2024-11-06
  • 通讯作者: 杨艳玲，电子信箱：organic.acid@vip.126.com
  • 基金资助:
    国家重点研发计划（2021YFC2700903，2022YFC2703401）；国家自然科学基金（82000850）

Abnormal uridine metabolism and the diagnosis and treatment of developmental and epileptic encephalopathy 50

  1. *Henan Children’s Neurodevelopment Engineering Research Center；Children’s Hospital Affiliated to Zhengzhou University；Henan Children’s Hospital；Zhengzhou Children’s Hospital，Zhengzhou  450018，China
  • Online:2024-10-06 Published:2024-11-06

摘要： 尿苷是一种嘧啶核苷，是嘧啶代谢的关键前体，存在于血浆和脑脊液中，虽然是一种简单小分子代谢物，在大分子合成、昼夜节律、炎症反应、抗氧化、衰老等多种生物过程中起着关键作用。尿苷代谢异常可导致多种疾病，以神经精神损害为主，一些患者合并乳清酸尿症。发育性癫痫性脑病50型是由于CAD基因缺陷导致的罕见常染色体隐性遗传病，多功能酶复合物（谷氨酰胺酰胺转移酶、氨甲酰磷酸合成酶2、二氢乳清酸酶和天冬氨酸转氨甲酰酶）活性下降，尿苷-5’-单磷酸从头合成障碍，典型临床三联征为难治性癫痫、红细胞生成障碍性贫血和智力运动发育落后伴倒退，CAD基因分析是诊断关键。发育性癫痫性脑病50型是一种可治疗的罕见病，如能早期诊断，口服尿苷，预后良好，如果未获得及时治疗，导致进行性脑萎缩，预后不良，甚至死亡。

关键词: 尿苷, CAD基因, 发育性癫痫性脑病50型, 乳清酸尿症, 罕见病

Abstract: Uridine，a pyrimidine nucleoside，is a key precursor in pyrimidine metabolism and is present in plasma and cerebrospinal fluid. Despite being a simple small molecule metabolite，it plays a crucial role in various biological processes，including macromolecule synthesis，circadian rhythm，inflammatory response，antioxidation，and aging.Abnormal uridine metabolism can lead to numerous diseases，primarily neuropsychiatric disorders， and some patients have orotic aciduria. Developmental and epileptic encephalopathy 50 is a rare autosomal recessive disorder caused by defects in the CAD gene，leading to decreased activity of the multifunctional enzyme complex（glutamine amidotransferase，carbamoyl-phosphate synthetase 2，dihydroorotase，and aspartate transcarbamylase，CAD）and impaired de novo synthesis of uridine-5'-monophosphate. The typical clinical triad includes refractory epilepsy，erythroblastopenia，and intellectual and motor developmental delay with regression.CAD gene analysis is crucial for diagnosis. Developmental and epileptic encephalopathy 50 is a treatable rare disease. Early diagnosis and oral uridine supplementation are keys to the good outcome. Without timely treatment，it can lead to progressive brain atrophy，poor prognosis，and even death.

Key words: uridine, CAD gene, developmental and epileptic encephalopathy 50, orotic aciduria, rare disease