Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up.
Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up.
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DOI：
10.1186/s13023-020-01630-2
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发表时间：
2021-01-07
影响因子：
3.7
通讯作者：
Morava E
中科院分区：
文献类型：
--
作者：
Starosta RT;Boyer S;Tahata S;Raymond K;Lee HE;Wolfe LA;Lam C;Edmondson AC;Schwartz IVD;Morava E
先天性糖基化异常(CDG)是一组罕见的多系统受累的异质性代谢性疾病。CDG的肝脏表型不仅根据具体疾病的不同而不同，而且在不同患者之间也不同。在这项研究中，我们试图确定广泛CDG患者中常见的肝损伤类型，并为临床实践中的随访提供建议。患者参加了先天糖基化疾病的自然病史研究。我们分析了39例患者的临床病史、分子遗传学、血清肝损伤标志物、肝脏超声和瞬时弹性成像、肝组织病理学(如果有)和临床评分，16种不同的CDG型(PMM2-CDG19例)，中位年龄7岁(范围：10个月至65岁)。对于可以通过特定干预措施治疗的疾病患者，我们增加了对治疗中肝脏参数的描述。我们的主要发现是(1)肝细胞损伤标志物丙氨酸氨基转移酶和天冬氨酸氨基转移酶随年龄的变化有明显的规律，尤其是在PMM2-CDG患者和其他CDG-I患者中，胆管细胞损伤标志物γ-谷氨酰转移酶在大多数患者中没有升高，表明肝细胞损伤是唯一的肝细胞损伤来源；(2)肝脏超声和瞬时弹性成像在肝纤维化征象之间存在明显的分离；(3)PMM2-CDG患者肝组织的组织病理学表现包括胞浆糖原沉积；以及(4)大多数CDG类型显示不止一种类型的肝损伤。基于这些发现，我们建议所有CDG患者定期进行系统、全面的肝病筛查，包括体检(肝脏肿大和肝功能衰竭迹象)、实验室检查(血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶)、肝脏超声(用于脂肪变性和肝肿瘤)和肝脏弹性成像(用于纤维化)。
The congenital disorders of glycosylation (CDG) are a heterogeneous group of rare metabolic diseases with multi-system involvement. The liver phenotype of CDG varies not only according to the specific disorder, but also from patient to patient. In this study, we sought to identify common patterns of liver injury among patients with a broad spectrum of CDG, and to provide recommendations for follow-up in clinical practice. Patients were enrolled in the Frontiers in Congenital Disorders of Glycosylation natural history study. We analyzed clinical history, molecular genetics, serum markers of liver injury, liver ultrasonography and transient elastography, liver histopathology (when available), and clinical scores of 39 patients with 16 different CDG types (PMM2-CDG, n = 19), with a median age of 7 years (range: 10 months to 65 years). For patients with disorders which are treatable by specific interventions, we have added a description of liver parameters on treatment. Our principal findings are (1) there is a clear pattern in the evolution of the hepatocellular injury markers alanine aminotransferase and aspartate aminotransferase according to age, especially in PMM2-CDG patients but also in other CDG-I, and that the cholangiocellular injury marker gamma-glutamyltransferase is not elevated in most patients, pointing to an exclusive hepatocellular origin of injury; (2) there is a dissociation between liver ultrasound and transient elastography regarding signs of liver fibrosis; (3) histopathological findings in liver tissue of PMM2-CDG patients include cytoplasmic glycogen deposits; and (4) most CDG types show more than one type of liver injury. Based on these findings, we recommend that all CDG patients have regular systematic, comprehensive screening for liver disease, including physical examination (for hepatomegaly and signs of liver failure), laboratory tests (serum alanine aminotransferase and aspartate aminotransferase), liver ultrasound (for steatosis and liver tumors), and liver elastography (for fibrosis).
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影响因子：
3.8
作者：
Mention, K.;Lacaille, F.;de Lonlay, P.
通讯作者：
de Lonlay, P.
影响因子：
13.5
作者：
Cannata Serio, Magda;Graham, Laurie A.;Lefeber, Dirk J.
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