AP-HP, Necker University Hospital, Hepatology and Gastroenterology Unit, French National Reference Centre for Biliary Atresia and Genetic Cholestasis, France; Paris Descartes University, France.
AP-HP, French National Reference Centre for Wilson Disease, Neurology Department, Lariboisière Hospital, Paris, France.
Mol Genet Metab. 2018 Jul;124(3):228-235. doi: 10.1016/j.ymgme.2018.05.002. Epub 2018 May 9.
Congenital disorders of glycosylation (CDG) linked to defects in Golgi apparatus homeostasis constitute an increasing part of these rare inherited diseases. Among them, COG-CDG, ATP6V0A2-CDG, TMEM199-CDG and CCDC115-CDG have been shown to disturb Golgi vesicular trafficking and/or lumen pH acidification. Here, we report 3 new unrelated cases of CCDC115-CDG with emphasis on diagnosis difficulties related to strong phenotypic similarities with mitochondriopathies, Niemann-Pick disease C and Wilson Disease. Indeed, while two individuals clinically presented with early and severe liver fibrosis and cirrhosis associated with neurological symptoms, the other one "only" showed isolated and late severe liver involvement. Biological results were similar to previously described patients, including hypercholesterolemia, elevated alkaline phosphatases and defects in copper metabolism. CDG screening and glycosylation study finally led to the molecular diagnosis of CCDC115-CDG. Besides pointing to the importance of CDG screening in patients with unexplained and severe liver disease, these reports expand the clinical and molecular phenotypes of CCDC115-CDG. The hepatic involvement is particularly addressed. Furthermore, hypothesis concerning the pathogenesis of the liver disease and of major biological abnormalities are proposed.
先天性糖基化障碍（CDG）与高尔基体稳态缺陷有关，构成了这些罕见遗传性疾病的重要组成部分。其中，COG-CDG、ATP6V0A2-CDG、TMEM199-CDG 和 CCDC115-CDG 已被证明会干扰高尔基体囊泡运输和/或内腔 pH 值酸化。在这里，我们报告了 3 例新的无关 CCDC115-CDG 病例，重点介绍了与线粒体病、尼曼-皮克病 C 和威尔逊病具有强烈表型相似性相关的诊断困难。事实上，虽然有 2 名患者临床上表现为早期和严重的肝纤维化和肝硬化，并伴有神经症状，但另一名患者“仅”表现为孤立的和晚期严重的肝脏受累。生物学结果与之前描述的患者相似，包括高胆固醇血症、碱性磷酸酶升高和铜代谢缺陷。CDG 筛查和糖基化研究最终导致了 CCDC115-CDG 的分子诊断。除了指出在不明原因和严重肝脏疾病的患者中进行 CDG 筛查的重要性外，这些报告还扩展了 CCDC115-CDG 的临床和分子表型。特别关注了肝脏受累的情况。此外，还提出了关于肝脏疾病和主要生物学异常的发病机制的假说。
