Mannose Phosphate Isomerase Deficiency-Congenital Disorder of Glycosylation (MPI-CDG) Type 1b: Familial Case of Thrombophilia and Liver Disorder

Extract

Clinical History and Background

A 14-year-old boy, born from consanguineous parents, presented with syncope and orbital floor fracture after head trauma, revealing multiterritorial ischemic stroke with hemorrhage. He had a history of recurrent fainting without loss of consciousness and surgery for aortic coarctation with ventricular septal defect.

Routine cardiac, gastroenterological, and neurological evaluations were normal. Biochemical tests identified decreased antithrombin III levels [77%; Normal(N) > 85%] and low transferrin saturation 0.05 (N: 0.20–0.50), while the autoimmune and extensive metabolic workups were normal.

Diagnosis and Discussion

Mannose phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) diagnosis was confirmed biochemically (Fig. 1) and genetically (likely pathogenic homozygous variant in MPI (the mannose phosphate isomerase gene) (NM_002435: c.21C>A, p.(Phe7Leu)).

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The patient’s glucose levels at fainting episodes and during 48-hour monitoring were normal. Mannose therapy at 3 grams 3 times daily resolved the fainting episodes. Genetic screening of the patient’s parents revealed the same homozygous variant in his father. Subsequent biochemical testing confirmed the diagnosis of MPI-CDG in the father, who reported abdominal pain. He previously lost his driving license after elevated carbohydrate-deficient transferrin (CDT) levels, falsely suggesting alcohol consumption. His antithrombin III level was 66% (N 80–120%).