Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management

Mol Genet Metab. 2023 Nov;140(3):107674. doi: 10.1016/j.ymgme.2023.107674. Epub 2023 Jul 31.

Abstract

Objectives: 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.

Methods: 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).

Results: 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.

Discussion: 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.

Conclusion: Acute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.

Keywords: Coagulation; Emergency protocol; Haemorrhages; PMM2-CDG; Stroke-like episodes; Thrombosis.

Publication types

  • Multicenter Study

MeSH terms

  • Antithrombins
  • Child
  • Congenital Disorders of Glycosylation* / pathology
  • Factor XI
  • Hemorrhage
  • Hemostasis
  • Humans
  • Phosphotransferases (Phosphomutases)* / deficiency
  • Protein C
  • Retrospective Studies
  • Stroke*
  • Thrombosis*

Substances

  • Protein C
  • Factor XI
  • Phosphotransferases (Phosphomutases)
  • Antithrombins

Supplementary concepts

  • Congenital disorder of glycosylation type 1A