Mannose phosphate isomerase deficiency‐congenital disorder of glycosylation (MPI‐CDG) with cerebral venous sinus thrombosis as first and only presenting symptom: A rare but treatable cause of thrombophilia

Abstract

Mannose phosphate isomerase deficiency‐congenital disorder of glycosylation (MPI‐CDG; formerly named CDG type 1b) is characterized by the clinical triad of hepatopathy, protein‐losing enteropathy, and hyperinsulinemic hypoglycemia in combination with coagulation disorder (thrombophilia, depletion of antithrombin, proteins C and S, factor XI). In the majority of patients, MPI‐CDG manifests during early infancy or childhood. Here, we present a 15‐year‐old female patient with unremarkable medical history suffering from acute cerebral venous sinus thrombosis necessitating interventional thrombectomy and neurosurgical decompression. Diagnostic work‐up of thrombophilia revealed deficiency of antithrombin (AT), proteins C and S, and factor XI. Detailed evaluation identified MPI‐CDG as the underlying cause of disease. After initiation of mannose therapy, coagulation parameters normalized. The girl fully recovered without any neurologic sequelae, and remains free of further thrombotic events or any other clinical and laboratory abnormalities on follow‐up 1 year after start of mannose treatment. In conclusion, we here present the significant case of MPI‐CDG with a severe cerebral venous sinus thrombosis as the first and only symptom of the disease. In light of the high frequency of AT deficiency on one hand, and the excellent treatability of MPI‐CDG on the other hand, CDG screening should be included as a routine analysis in all patients presenting with unexplained coagulation disorder, especially when comprising AT deficiency.

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

“…Interestingly, MPI-CDG symptoms are atypical by comparison to other disorders in the CDG family of disorders, which are described later, and show a marked lack of neurological pathophysiology [ 80 , 83 , 88 ]. MPI-CDG patients, of which 35 have been described as of 2020, present with an established triad of hepatic, gastroenterological, and endocrine symptoms [ 89 , 90 ] ( Table 1 ).…”

Mannose phosphate isomerase gene mutation leads to a congenital disorder of glycosylation: A rare case report and literature review

“…Notably, the age of the patient was similar to that reported in the literature review, as disease onset occurred below 2 years of age in the majority of the patients (43/50). MPI-CDG usually involves the digestive and endocrine systems, and it presents with a “classic triad” consisting of hepatic (liver fibrosis, hepatopathy), gastroenterological (diarrhea, protein-losing enteropathy), and endocrine (hyperinsulinemic-hypoglycemia) involvement ( 6 ), but the clinical picture varies among cases. This phenomenon might be because MPI enzyme activity varies among MPI-CDG patients.…”

“…These include venous thrombosis and abnormally elevated leukocyte levels. In fact, among the 52 patients with MPI-CDG, 12 had a history of thrombosis, including jugular vein thrombosis, deep venous thrombosis, and intracranial thrombosis ( 6 , 21 , 22 ). In humans, the liver produces the majority of coagulation factors.…”

Liver Involvement in Congenital Disorders of Glycosylation and Deglycosylation

“…Coagulation abnormalities require a special attention in CDG. They typically affect both procoagulant and anticoagulant factors, in the case of which antithrombin deficiency, protein C and S deficiency, and factor XI deficiency were mainly observed, respectively ( 1 – 3 , 50 – 53 ). Elevated serum transaminases observed in the majority of our CDG patients were associated with the presence of coagulation disorders, including protein C, protein S, and antithrombin deficiency.…”