Abstract：
The Ehlers-Danlos syndromes are a group of multisystemic heritable connective tissue disorders with clinical presentations that range from multiple congenital malformations, over adolescent-onset debilitating or even life-threatening complications of connective tissue fragility, to mild conditions that remain undiagnosed in adulthood. To date, thirteen different EDS types have been recognized, stemming from genetic defects in 20 different genes. While initial biochemical and molecular analyses mainly discovered defects in genes coding for the fibrillar collagens type I, III and V or their modifying enzymes, recent discoveries have linked EDS to defects in non-collagenous matrix glycoproteins, in proteoglycan biosynthesis and in the complement pathway. This genetic heterogeneity explains the important clinical heterogeneity among and within the different EDS types. Generalized joint hypermobility and skin hyperextensibility with cutaneous fragility, atrophic scarring and easy bruising are defining manifestations of EDS; however, other signs and symptoms of connective tissue fragility, such as complications of vascular and internal organ fragility, orocraniofacial abnormalities, neuromuscular involvement and ophthalmological complications are variably present in the different types of EDS. These features may help to differentiate between the different EDS types but also evoke a wide differential diagnosis, including different inborn errors of metabolism. In this narrative review, we will discuss the clinical presentation of EDS within the context of inborn errors of metabolism, give a brief overview of their underlying genetic defects and pathophysiological mechanisms and provide a guide for the diagnostic approach.
摘要：
Ehlers-Danlos综合征是一组多系统遗传性结缔组织疾病，临床表现包括多种先天性畸形，超过青少年发作的结缔组织脆性衰弱甚至危及生命的并发症，成年后仍未诊断的轻度疾病。迄今为止,已经认识到13种不同的EDS类型，源于20个不同基因的遗传缺陷。虽然最初的生化和分子分析主要发现了I型纤维状胶原蛋白编码基因的缺陷，III和V或它们的修饰酶，最近的发现将EDS与非胶原基质糖蛋白的缺陷联系起来，在蛋白聚糖生物合成和补体途径中。这种遗传异质性解释了不同EDS类型之间和内部的重要临床异质性。广义的关节活动过度和皮肤过度扩张伴皮肤脆性，萎缩性疤痕和容易瘀伤是EDS的定义表现；然而，结缔组织脆性的其他体征和症状，如血管和内脏器官脆性的并发症，口颜面异常,神经肌肉受累和眼科并发症在不同类型的EDS中存在差异。这些特征可能有助于区分不同的EDS类型，但也引起广泛的鉴别诊断。包括不同的先天代谢错误。在这篇叙述性评论中，我们将在先天性代谢错误的背景下讨论EDS的临床表现，简要概述其潜在的遗传缺陷和病理生理机制，并为诊断方法提供指导。
