Activity values of the enzyme phosphomanomutase 2 for diagnosing the CDG Ia glycosylation defect.

Introduction: Congenital disorders of glycosylation (CDG) are biochemically characterized by abnormal carbohydrate assembly. These disorders can result from mutations in the genes encoding different enzymes, leading to a partial or complete reduction in catalytic activity. They can be inherited in an autosomal recessive, dominant, or X-linked manner. Approximately 130 congenital disorders are currently known, within a multisystemic clinical spectrum with high heterogeneity between family members and between different types of CDG. Deficiencies of the cytosolic enzyme phosphomannomutase 2 (PMM2, E.C.5.4.2.8) cause a type-Ia glycosylation defect (PMM2-CDG or CDG Ia), which results in neurological damage, coagulation disorders, and gastrointestinal, hepatic, cardiac, and ocular problems, among others. This enzyme catalyzes the isomerization of mannose-6-phosphate to mannose-1-phosphate.

Objective: Our aim was to determine PMM2 activity levels using a microspectrophotometric method.

Materials And Methods: We collected 50 whole blood samples from healthy volunteer donors, including 24 females and 26 males aged 1.94-26. Leukocytes were extracted using the dextran-heparin method and then lysed. Moreover, protein was quantified via the Folin-Lowry method. We used the Van Schaftingen and Jaeken method, which we modified and standardized.

Results: The study established a reference value of 6.546-48.023 nmol/h*mg protein for PMM2.

Conclusion: This study allowed detecting a 24-day-old girl with CDG Ia who showed no residual phosphomannomutase 2 activity.