Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark; Department for Regional Health Services, University of Southern Denmark, Odense, Denmark.
The Epilepsy Clinic, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Epilepsy Res. 2021 Feb;170:106530. doi: 10.1016/j.eplepsyres.2020.106530. Epub 2020 Dec 9.
Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality. This study aimed to evaluate the observed high mortality and the causes of death in PIGA-CDG patients.
We reviewed the literature and collected additional unpublished patients through an international network.
In total, we reviewed the data of 88 patients of whom 30 patients born alive were deceased, and the overall mortality before the age of 20 years was 30 % (26/88). Age at death ranged from 15 days to 48 years of life. The median age at death was two years and more than half of the patients deceased in early childhood. The PIGA-specific mortality rate/1000 person-years was 44.9/1000 person-years (95 %, CI 31.4-64.3). There were no cases of definite or probable sudden unexpected death in epilepsy (SUDEP) and half of the patients died due to respiratory failure (15/30, 50 %) or possible SUDEP (3/30, 10 %). Three patients (10 %) died from severe cardiomyopathy, liver failure and gastrointestinal bleeding, respectively. The cause of death was unclassified in nine patients (30 %). Autopsies were rarely performed and the true cause of death remains unknown for the majority of patients.
Our data indicate an increased risk of premature death in patients with PIGA-CDG when compared to most monogenic developmental and epileptic encephalopathies.
由于磷脂酰肌醇聚糖锚生物合成 A 类蛋白（PIGA）缺陷导致的先天性糖基化障碍（CDG）是一种严重的 X 连锁发育性和癫痫性脑病。癫痫发作通常难以治疗，患者存在智力残疾和全面发育迟缓。先前的报告表明，PIGA-CDG 患者有过早死亡的高风险。本研究旨在评估 PIGA-CDG 患者观察到的高死亡率和死亡原因。
我们回顾了文献，并通过国际网络收集了额外的未发表患者数据。
我们共回顾了 88 例患者的数据，其中 30 例存活出生的患者已死亡，20 岁前的总死亡率为 30%（26/88）。死亡年龄从 15 天到 48 岁不等。死亡的中位数年龄为 2 岁，超过一半的患者在儿童早期死亡。PIGA 特异性死亡率/1000 人年为 44.9/1000 人年（95%CI 31.4-64.3）。无明确或可能的癫痫性猝死（SUDEP）病例，半数患者因呼吸衰竭（15/30，50%）或可能的 SUDEP（3/30，10%）而死亡。三名患者（10%）分别死于严重心肌病、肝功能衰竭和胃肠道出血。9 名患者（30%）的死因未分类。很少进行尸检，大多数患者的真正死因仍不清楚。
与大多数单基因发育性和癫痫性脑病相比，我们的数据表明 PIGA-CDG 患者有过早死亡的风险增加。
