Long-term follow-up and sudden unexpected death in Gaucher disease type 3 in Egypt.
Long-term follow-up and sudden unexpected death in Gaucher disease type 3 in Egypt.
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DOI：
10.1212/nxg.0000000000000055
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Schiffmann R
中科院分区：
文献类型：
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作者：
Abdelwahab M;Blankenship D;Schiffmann R
描述在埃及接受酶替代治疗（ERT）的3型戈谢病患者的长期随访和不同表型。一项对78例接受ERT治疗的患者进行的前瞻性队列研究，这些患者接受了长达9年的随访，每年进行一次评估，包括EEG和认知测试。73%的患者为L444 P GBA 1突变纯合子;除7例外，所有患者均有神经系统症状。91%的患者存在核上性凝视麻痹，认知功能变化但稳定。会聚性斜视和眼球功能障碍分别为22%和37%。54%的患者存在对立违抗性障碍的特征。23例患者（30%）在接受ERT治疗1-9年期间发生癫痫发作。其中，12例患者（15%）突然意外死亡，平均年龄为6.7 ± 5.0岁（范围1.5-18岁）。猝死通常与癫痫发作或终末癫痫发作有关，但12例患者中有7例先前EEG正常。另外11%的患者在EEG上有背景减慢或致癫痫活动，但无临床癫痫发作。3例家族性猝死。尽管具有已知与神经病理性戈谢病相关的最常见的GBA 1基因型，但埃及的戈谢病3型患者的表型和ERT的临床结果与其他人群中观察到的结果非常不同。确定这个种族群体的假定修饰基因可能会导致更好的治疗神经病变性戈谢病一般。
To describe the long-term follow-up and distinct phenotype of a large cohort of patients with Gaucher disease type 3 on enzyme replacement therapy (ERT) in Egypt. A prospective cohort study of 78 patients on ERT who were followed for up to 9 years with yearly evaluations that included EEG and cognitive testing. Of the patients, 73% were homozygous for the L444P GBA1 mutation; all but 7 were neurologically symptomatic. Supranuclear gaze palsy with variable but stable cognitive function was present in 91% of patients. Convergent strabismus and bulbar dysfunction were noted in 22% and 37%, respectively. Features of oppositional defiant disorder were present in 54% of patients. Twenty-three patients (30%) developed seizures while on ERT for 1–9 years. Of those, 12 patients (15%) died suddenly and unexpectedly at a mean age of 6.7 ± 5.0 years (range 1.5–18). Sudden death was usually associated with a seizure disorder or a terminal seizure, but 7 of 12 patients had a preceding normal EEG. An additional 11% had background slowing or epileptogenic activity on EEG without clinical seizures. There were 3 familial cases of sudden unexpected death. Despite having the most common GBA1 genotype known to be associated with neuronopathic Gaucher disease, patients with Gaucher disease type 3 in Egypt have a phenotype and a clinical outcome on ERT that are very different from those observed in other populations. Identifying putative modifying genes of this ethnic group is likely to lead to better therapy for neuronopathic Gaucher disease generally.