Diagnosis

Establish or confirm diagnosis

Diagnosing congenital disorders of glycosylation Ia (phosphomannomutase-2 deficiency: CDG-Ia or PMM2-CDG) and Ib (phosphomannose isomerase deficiency: CDG-Ib or MPI-CDG). Follow-up testing for patients with an abnormal transferrin isoform profile. This test is not useful for carrier testing.

Leukocytes are harvested from one 7-mL tube of ACD-treated blood and the resulting leukocyte cell pellet is subjected to 1 freeze-thaw cycle. The lysate is collected and the enzymatic activity for both phosphomannomutase and phosphomannose isomerase is measured by a colorimetric assay.(Personal communication: Dr. Otto van Diggelen, Erasmus University, Rotterdam, … Leukocytes are harvested from one 7-mL tube of ACD-treated blood and the resulting leukocyte cell pellet is subjected to 1 freeze-thaw cycle. The lysate is collected and the enzymatic activity for both phosphomannomutase and phosphomannose isomerase is measured by a colorimetric assay.(Personal communication: Dr. Otto van Diggelen, Erasmus University, Rotterdam, The Netherlands 2008; Cowan T, Pasquali M: Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw Hill Education; 2017:1139-1158) View more

Tests performed
Entire test performed in-house

Accuracy was assessed by analysis of positive and negative samples; 100% clinical concordance was achieved.Intra assay precision was performed at 3 levels: CV results ranged from 3.9%-18.8% (N=20 each). Inter assay precision was performed at 3 levels: CV results ranged from 6.1%-25.1% (N=20 each). The analytical measurement range is enzyme … Accuracy was assessed by analysis of positive and negative samples; 100% clinical concordance was achieved.Intra assay precision was performed at 3 levels: CV results ranged from 3.9%-18.8% (N=20 each). Inter assay precision was performed at 3 levels: CV results ranged from 6.1%-25.1% (N=20 each). The analytical measurement range is enzyme dependent and ranges from 0-61,211 nmol/hr/mg. View more

There are some known carriers of phosphomannomutase-2 deficiency (PMM2) who have reduced enzyme activity that falls in the range of affected patients with PMM2-congenital disorders of glycosylation (CDG). The PMM2 enzyme result should be considered along with CDG transferrin, clinical phenotype, and genotype when determining a diagnosis.

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Intra-Laboratory

Description of PT method: Help
Intra-laboratory alternative assessment of performance through quality control or patient blind testing

Description of internal test validation method: Help
This test was laboratory developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements.