Mohamed M, Guillard M, Wortmann S B, Cirak S, Marklova E, Michelakakis H, Korsch E, Adamowicz M, Koletzko B, van Spronsen F J, Niezen-Koning K E, Matthijs G, Gardeitchik T, Kouwenberg D, Lim B Chan, Zeevaert R, Wevers R A, Lefeber D J, Morava E
Institute for Genetic and Metabolic Diseases at the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Biochim Biophys Acta. 2011 Jun;1812(6):691-8. doi: 10.1016/j.bbadis.2011.02.011. Epub 2011 Mar 17.
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.
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障碍的常见症状，包括几种最近发现的与高尔基体相关的糖基化缺陷。为了寻找鉴别特征，我们评估了11名疑似患有与高尔基体相关的先天性糖基化缺陷的儿童。我们对所有基因未解决的患者进行了评估，这些患者在1999年至2009年期间被诊断为2型转铁蛋白等聚焦模式。通过将生化结果与特征性临床症状相结合，我们使用诊断流程图来探讨先天性糖基化障碍-IIx患者的潜在缺陷。根据特定症状和实验室结果，我们开展了额外的、有针对性的生化和基因研究。我们发现了一系列独特的2型先天性糖基化障碍相关异常，包括突发性听力丧失、脑畸形、皮肤起皱和癫痫，同时伴有骨骼发育不良、扩张型心肌病、心脏骤停、铜和铁代谢异常以及内分泌异常。一名患有严重皮质畸形和轻度皮肤异常的患者被诊断为一种已知的遗传综合征，病因是ATP6V0A2缺陷。在此，我们介绍了独特的2型先天性糖基化障碍相关异常，包括与ATP酶相关和不相关的皮肤松弛症以及感觉神经性听力丧失，这是先天性糖基化障碍最近才被认识到的一种症状。基于我们的发现，我们建议临床医生，即使在没有智力残疾的情况下，对于患有心律失常、脊椎发育不良以及铜和铁代谢生化异常的患者，也应考虑先天性糖基化障碍。
