Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern
Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern
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DOI：
10.1016/j.bbadis.2011.02.011
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发表时间：
2011-06-01
影响因子：
6.2
通讯作者：
Morava, E.
中科院分区：
文献类型：
--
作者：
Mohamed, M.;Guillard, M.;Morava, E.
畸形特征、多系统疾病和中枢神经系统受累是先天性糖基化疾病的常见症状，包括最近发现的几种高尔基体相关糖基化缺陷。为了寻找区分特征，我们评估了11名疑似患有Golgi相关先天性糖基化错误的儿童。我们评估了1999-2009年期间所有遗传学未解决的患者，诊断为2型转铁蛋白等聚焦模式。通过结合生化结果与特征性临床症状，我们使用了诊断流程图来探讨先天性糖基化-IIx疾病患者的潜在缺陷。根据具体症状和实验室结果，我们启动了额外的、有针对性的生化和遗传研究。我们在患者中发现了一系列独特的糖基化2型相关异常的先天性疾病，包括突发性听力损失、脑畸形、皮肤皱纹和癫痫，并伴有骨骼发育不良、扩张型心肌病、心脏骤停、铜和铁代谢异常以及内分泌异常。1例严重皮质畸形和轻度皮肤异常的患者被诊断为已知的遗传综合征，由于ATP 6V 0A 2缺陷。在此，我们提出了独特的先天性糖基化疾病2型相关异常，包括ATP酶相关和不相关的皮肤松弛和感音神经性听力损失，这是最近认识到的先天性糖基化疾病的症状。根据我们的研究结果，我们建议临床医生考虑先天性糖基化障碍患者的心律失常，脊椎发育不良和生化异常的铜和铁代谢，即使在没有智力残疾。(C)2011爱思唯尔有限公司版权所有。
Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability. (C) 2011 Elsevier B.V. All rights reserved.