Carbohydrate Glycosylation Deficiency Disorder Secondary to Absence of Phosphomannose Mutase Confers Both a Hemorrhagic and Thrombotic Phenotype

Abstract

Congenital disorders of glycosylation are a group of inherited disorders affecting the addition of a carbohydrate moiety to a protein. A defect in this pathway can cause adverse effects in most organ systems, often presenting early in life. The most common of these disorders is CDG type 1a / PMM2-CDG). In this disorder the loss of the enzyme phosphomannomutase-2 prevents the conversion of mannose-6-phosphate to mannose-1-phosphate. This has previously been associated with deficiencies of protein C, protein S, antithrombin III, factor IX and factor XI and a subsequent imbalance of coagulation pathways leading to thrombotic events.We present the case of a 14-year-old male with known history of CDG1a and previous bleeding complications following left orchiopexy at age 3, at that time coagulation screening showed a normal PT/PTT and surgery was deemed safe. The patient now presented to our pediatric hematology/oncology clinic for further evaluation of coagulation abnormalities prior to pediatric surgery performing right orchiopexy. Laboratory values at this time showed coagulation deficiencies, of ATIII, Factor XI, Protein C and Protein S, PT/ PTT , F VIII, FIX and vWF where normal. Prior to surgery, patient was given fresh frozen plasma and ATIII concentrate the patient underwent a successful Stage One Fowler-Stephen Procedure with adequate hemostasis. Several months later the patient developed leg swelling and was diagnosed right femoral DVT. This resolved with ATIII substitution and anticoagulation with LMW heparin. The patient's immediate family was tested for bleeding/clotting disorders and results were found to be normal. This report not only supports the association of bleeding but also thrombosis with CDG1a. We propose that in patients with known CDG routine PT/PTT will not uncover a hemostatic abnormality but further screening isolated factor deficiency need to be performed and prophylactic factor substitution be performed prior to any surgical interventions. Also an awareness of the highly procoagulant state in these patients that predispose to DVT and central nervous system vascular thrombosis need to be present. DisclosuresNo relevant conflicts of interest to declare.