Journal Article

P14 Congenital disorder of glycosylation ib type (CDG IB): 2 cases of diagnostics and treatment

Migali, AV, Zhurkova, NV, Akoev, YuS, Mitish, MD, Kazakova, KA, Studenikin, VM

2017

Overview

CDG Ib type is a rare autosomal recessive disorder (OMIM 154550) manifesting as coagulopathy, hypoglycemia, enteropathy, liver damage, delayed physical development etc. Approximately 20 cases of CDG Ib are described world-wide, being one of two CDG types, responding to treatment (along with CDG IIc type). CDG Ib is caused by a mutation in mannose-6-phosphate isomerase. Then, mannose-6-phosphate for protein N-glycosylation can only be synthesised from outside sources mannose. Treatment with d-mannose is the only described therapy for CDG Ib. We have extablished the diagnosis in 2 patients. Patient 1 was a 9 months old girl with exudative enteropathy, hypoproteinemia, ascites, liver fibrosis, malabsorption, multiple deficiency syndrome, hypoglycemia, coagulopathy with low antithrombin III and protein C, and right atrium thrombosis. Patient 2 was a 10 months old boy with severe physical delay and liver damage. Coagulogram studies showed low antithrombin III/protein C levels. The diagnosis was proved by molecular genetics and biochemistry in both cases. Mutation in mannose-6-phospahte isomerase gene (Ar219Trp – R219W) and abnormally structured glycoproteins (transferrin, α1-antitrypsin, haptoglobin) were discovered in patient 1. Mutation c.1252T>C in homozygotic state was found in MPI gene of patient 2. Treatment with d-mannose (150 mg/kg) resulted in stool normalisation, albumin, glucose, antithrombin III and protein C levels’ increase, intoxication symptoms and clot’s disappearance in 2 weeks. Frequent episodes of acute respiratory infections with manifested CDG symptoms demanded the increase of d-mannose (up to 230 mg/kg). The therapy revealed no side effects. Normal glucose, albumin and antithrobmin III were the criteria for adequate dose selection. We conclude that CDG Ib should be considered in patients with unexplained chronic diarrhoea, hypoglycemia, liver pathology, thromboses/haemorrhages, allowing early diagnostics/effective management for this rare disorder.

• Publisher: BMJ Publishing Group LTD
• Subject: A1-antitrypsin / Albumin / Antithrombin / Ascites / Diagnosis / Diarrhea / Fibrosis / Genetics / Glycoproteins / Glycosylation / Haptoglobin / Hemorrhage / Hereditary diseases / Hypoglycemia / Intoxication / Liver / Malabsorption / Mannose / Mannose-6-phosphate isomerase / Mpi gene / Mutation / Pediatrics / Physical Development / Protein C / Proteins / Respiratory tract infection / Thromboembolism / Thrombosis