尿苷代谢异常与发育性癫痫性脑病50型的诊断与治疗

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

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。

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 encephalopathy50 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.