Gadomski Therese E, Bolton Melody, Alfadhel Majid, Dvorak Chris, Ogunsakin Olalekan A, Nelson Stephen L, Morava Eva
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana.
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana.
Am J Med Genet A. 2017 Oct;173(10):2772-2775. doi: 10.1002/ajmg.a.38377. Epub 2017 Aug 4.
ALG13-CDG has been recently discovered as a disorder of severe developmental, intellectual and speech disability, microcephaly, visual abnormalities, seizures, hepatomegaly, coagulation abnormalities, and abnormal serumtransferrin isoelectric focusing in serum. A male with seizures, delayed motor, and speech development, but normal cognition carried a hemizygous, predicted pathogenic ALG13 variant (p.E463G). N-glycosylation studies in plasma were normal. ICAM-1 expression was decreased in patient fibroblasts, supporting the variant's pathogenicity. Adding D-galactose to the patient's fibroblast culture increased ICAM-1 expression in vitro, offering a potential treatment option in ALG13-CDG. The present report is a new example for an N-glycosylation disorder, that may present with normal transferrin isoform analysis, and also demonstrates, that CDG type I patients can have normal cognitive development.
最近发现，ALG13 - CDG是一种严重的发育、智力和语言障碍疾病，伴有小头畸形、视觉异常、癫痫发作、肝肿大、凝血异常以及血清中转铁蛋白等电聚焦异常。一名患有癫痫发作、运动和语言发育迟缓但认知正常的男性携带一个半合子、预测为致病性的ALG13变异体（p.E463G）。血浆中的N - 糖基化研究结果正常。患者成纤维细胞中ICAM - 1表达降低，支持该变异体的致病性。在患者的成纤维细胞培养物中添加D - 半乳糖可在体外增加ICAM - 1表达，为ALG13 - CDG提供了一种潜在的治疗选择。本报告是N - 糖基化障碍的一个新例子，该疾病可能表现为转铁蛋白异构体分析正常，同时也证明了I型先天性糖基化障碍（CDG）患者的认知发育可能正常。
