OBJECTIVE Asparagine-linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis. METHODS We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants. RESULTS The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one-half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one-third of all cases paroxysms of fast activity with electrodecrement. ALG13-related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one-third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired. SIGNIFICANCE X-linked ALG13-related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.

中文翻译：

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X 连锁婴儿型 ALG13 相关发育性和癫痫性脑病的表型谱

目标天冬酰胺连接的糖基化 13 (ALG13) 缺陷在具有发育性和癫痫性脑病 (DEE) 的临床表型的文献中被反复描述。大多数病例是携带复发性 ALG13 de novo 变体 p.(Asn107Ser) 的女性，转铁蛋白电泳正常。方法 我们描绘了 38 个个体的表型谱，37 个女孩和一个男孩，其中 16 个是新的，22 个已发表，具有最常见的致病性 ALG13 变异 p.（Asn107Ser），并另外报告了三个携带其他可能致病性 ALG13 变异的个体的表型. 结果 表型谱通常包括伴有癫痫痉挛的药物耐药性癫痫，大多数在生命的前 6 个月内发病，一半的病例痉挛持续存在。强直性癫痫发作是最常见的额外癫痫发作类型。脑电图显示，在所有病例中，三分之一的病例在疾病晚期出现高度心律失常和快速活动性发作，并伴有电分泌物。ALG13 相关的 DEE 通常与严重到严重的发育迟缓有关；三分之一的病例获得了走动，而有目的的手部使用很少或完全不存在。手的刻板印象和运动障碍包括肌张力障碍或舞蹈手足徐动症相对频繁。语言沟通技巧缺失或较差，眼神交流和追求往往受损。意义 X 连锁 ALG13 相关的 DEE 通常表现为 West 综合征，伴有严重到严重的发育迟缓。它主要是由反复出现的从头错义变异 p.(Asn107Ser) 引起的。