Abstract：
BACKGROUND: CAD (MIM*114010) encodes a large multifunctional protein with the enzymatic activity of the first three enzymes initiating and controlling the de novo pyrimidine biosynthesis pathway. Biallelic pathogenic variants in CAD cause the autosomal recessive developmental and epileptic encephalopathy 50 (MIM #616457) or CAD deficiency presenting with epilepsy, status epilepticus (SE), neurological deterioration and anemia with anisopoikilocytosis. Mortality is around 9% of patients, mainly related to the no use of its specific treatment with uridine. Majority of reported cases have an early onset during infancy, with some few starting later in childhood.
METHODS: Here we report a deceased female patient with CAD deficiency whose epilepsy started at 14 years. She showed a rapid neurologic deterioration including cognitive decline, electroencephalographic background slowing which later evolved to a fatal refractory SE and supra and infratentorial atrophy on neuroimaging. Anemia developed after SE onset.
RESULTS: her post-mortem whole exome sequencing identified biallelic missense variants in CAD (NM_004341.5): c.[2944G > A];[5366G > A] p.[(Asp982Asn)];[(Arg1789Gln)]. Our review of twenty-eight reported cases (2015-2023) revealed an epilepsy age onset from neonatal period to 7 years and the SE prevalence of 46 %.
CONCLUSIONS: With our case, we highlight the relevance of suspecting this treatable condition in older patients and in SE with no evident etiology.
METHODS: Here we report a deceased female patient with CAD deficiency whose epilepsy started at 14 years. She showed a rapid neurologic deterioration including cognitive decline, electroencephalographic background slowing which later evolved to a fatal refractory SE and supra and infratentorial atrophy on neuroimaging. Anemia developed after SE onset.
RESULTS: her post-mortem whole exome sequencing identified biallelic missense variants in CAD (NM_004341.5): c.[2944G > A];[5366G > A] p.[(Asp982Asn)];[(Arg1789Gln)]. Our review of twenty-eight reported cases (2015-2023) revealed an epilepsy age onset from neonatal period to 7 years and the SE prevalence of 46 %.
CONCLUSIONS: With our case, we highlight the relevance of suspecting this treatable condition in older patients and in SE with no evident etiology.
摘要：
背景：CAD（MIM*114010）编码一种大的多功能蛋白，具有前三种酶的酶活性启动和控制从头嘧啶生物合成途径。CAD中的双等位基因致病变异导致常染色体隐性遗传发育和癫痫性脑病50（MIM#616457）或表现为癫痫的CAD缺陷，癫痫持续状态（SE），神经系统恶化和贫血与异细胞增多症。死亡率约为9%的患者，主要与未使用尿苷的特异性治疗有关。大多数报告的病例在婴儿期早期发病，有些人从小就开始了。
方法：在这里，我们报告了一名患有CAD缺陷的女性患者，其癫痫发作于14岁。她表现出迅速的神经系统恶化，包括认知能力下降，脑电图背景减慢，后来演变成致命的难治性SE和神经影像学上的上和幕下萎缩。SE发作后出现贫血。
结果：她的死后全外显子组测序鉴定了CAD中的双等位基因错义变异（NM_004341.5）：c.[2944G>A]；[5366G>A]p.[（Asp982Asn）]；[（Arg1789Gln）]。我们对28例报告病例（2015-2023年）的审查显示，从新生儿期到7岁的癫痫发作年龄和SE患病率为46％。
结论：在我们的案例中，我们强调了怀疑这种可治疗疾病在老年患者和无明显病因的SE中的相关性.
方法：在这里，我们报告了一名患有CAD缺陷的女性患者，其癫痫发作于14岁。她表现出迅速的神经系统恶化，包括认知能力下降，脑电图背景减慢，后来演变成致命的难治性SE和神经影像学上的上和幕下萎缩。SE发作后出现贫血。
结果：她的死后全外显子组测序鉴定了CAD中的双等位基因错义变异（NM_004341.5）：c.[2944G>A]；[5366G>A]p.[（Asp982Asn）]；[（Arg1789Gln）]。我们对28例报告病例（2015-2023年）的审查显示，从新生儿期到7岁的癫痫发作年龄和SE患病率为46％。
结论：在我们的案例中，我们强调了怀疑这种可治疗疾病在老年患者和无明显病因的SE中的相关性.
