Wicker Camille, Roux Charles-Joris, Goujon Louise, de Feraudy Yvan, Hully Marie, Brassier Anais, Bérat Claire-Marine, Chemaly Nicole, Wiedemann Arnaud, Damaj Lena, Abi-Warde Marie-Thérèse, Dobbelaere Dries, Roubertie Agathe, Cano Aline, Arion Alina, Kaminska Anna, Da Costa Sabrina, Bruneel Arnaud, Vuillaumier-Barrot Sandrine, Boddaert Nathalie, Pascreau Tiffany, Borgel Delphine, Kossorotoff Manoelle, Harroche Annie, de Lonlay P
Centre de Référence des Maladies Héréditaires du Métabolisme, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Necker-Enfants-Malades, Institut Imagine, G2M, MetabERN, Paris, France; Centre de Compétence des Maladies Héréditaires du Métabolisme, Hôpital Universitaire de Strasbourg, Strasbourg, France.
Université Paris Cité, Paris, France; Service de Radiologie Pédiatrique, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Necker-Enfants-Malades, Institut Imagine, Paris, France.
Mol Genet Metab. 2023 Nov;140(3):107674. doi: 10.1016/j.ymgme.2023.107674. Epub 2023 Jul 31.
Patients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines.
In this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or "stroke mimic" (SM: normal brain imaging or evoking a migraine).
Thirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found.
Acute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy.
Acute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.
患有PMM2-CDG的患者会发生与凝血因子（因子XI）和凝血抑制剂（抗凝血酶、蛋白C和蛋白S）缺乏相关的急性事件（类中风发作（SLEs）、血栓形成、出血、癫痫发作、偏头痛）。本研究的目的是将急性事件与止血相关联并提出实用指南。
在这项多中心回顾性研究中，我们评估了因急性事件住院的PMM2-CDG患者的临床、放射学、止血和脑电图数据。脑部事件分为血栓形成、出血、SLE或“类中风”（SM：脑部影像正常或引发偏头痛）。
13名患者共有31次急性发作：27次脑部事件，其中7次SLE、4次静脉血栓形成、4次出血（3次与血栓形成相关）、15次SM，平均年龄为7.7岁；4次非脑部血栓形成，其中1次包括出血。经常有诱因（感染、头部创伤）。尽管有时在基线状态下正常，但因子XI、抗凝血酶和蛋白C水平在这些发作期间会下降。未发现止血异常与急性事件类型之间存在相关性。
PMM2-CDG中的急性事件不容忽视，且与止血异常相关。针对其预防和治疗提出了一项紧急方案（https://www.filiere-g2m.fr/urgences）。对于脑部事件，采用灌注加权成像和扩散序列的脑部磁共振成像、脑电图和止血蛋白水平可指导治疗：抗凝、补充抗凝血酶或新鲜冷冻血浆、抗癫痫治疗。在手术、长期制动、激素替代治疗的情况下，需要预防出血和血栓形成。
PMM2-CDG中的急性事件与止血异常相关，需要实用指导。
