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Test ID: PMMIL Phosphomannomutase (PMM) and Phosphomannose Isomerase (PMI), Leukocytes

Reporting Name

PMM-PMI, Leukocytes

Useful For

Diagnosing congenital disorders of glycosylation Ia (phosphomannomutase-2 deficiency: CDG-Ia or PMM2-CDG) and Ib (phosphomannose isomerase deficiency: CDG-Ib or MPI-CDG) as measured in leukocytes

 

Follow-up testing for patients with an abnormal transferrin isoform profile as determined by liquid chromatography-mass spectrometry (CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum)

Specimen Type

Whole Blood ACD


Advisory Information


The initial screening test for congenital disorders of glycosylation is transferrin isoform analysis (CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum). The results of the transferrin isoform analysis should be correlated with the clinical presentation to determine the most appropriate testing strategy, which may include this test (PMMIL).



Shipping Instructions


For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerated within 48 hours of draw to be stabilized. Draw specimen Monday through Thursday only and not the day before a holiday. Specimen should be drawn and packaged as close to shipping time as possible.



Specimen Required


Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A)

Specimen Volume: 6 mL

Collection Instructions: Do not transfer blood to other containers.


Specimen Minimum Volume

3 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood ACD Refrigerated 48 hours

Reference Values

PHOSPHOMANNOMUTASE

Normal >350 nmol/h/mg protein

 

PHOSPHOMANNOSE ISOMERASE

Normal >1,300 nmol/h/mg protein

Day(s) and Time(s) Performed

Varies

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

82657

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PMMIL PMM-PMI, Leukocytes In Process

 

Result ID Test Result Name Result LOINC Value
50836 Specimen 31208-2
50837 Specimen ID 57723-9
50838 Source 31208-2
50839 Order Date 82785-7
50840 Reason For Referral 42349-1
50841 Method 49549-9
50842 Phosphomannomutase, Leuko 78970-1
50843 Phosphomannose Isomerase, Leuko 78963-6
50844 Interpretation 59462-2
50845 Amendment 48767-8
50846 Reviewed By 18771-6
50847 Release Date 82772-5

Clinical Information

Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndrome, are a group of inherited metabolic diseases that affect one of the steps of the pathway involved in glycosylation. CDG typically present as multisystemic disorders and may include developmental delay, hypotonia, abnormal magnetic resonance imaging (MRI) findings, hypoglycemia, and protein-losing enteropathy. There is considerable variation in the severity of this group of diseases, which can range from hydrops fetalis to a mild presentation in adults. In some subtypes (Ib, in particular) intelligence is not compromised.

 

Phosphomannomutase-2 deficiency (PMM2-CDG or CDG-Ia) is an autosomal recessive glycosylation disorder resulting from reduced or absent activity of the enzyme phosphomannomutase-2, encoded by the PMM2 gene. It is the most common CDG worldwide. Patients with CDG-Ia have moderate to severe neurological disease, more or less typical dysmorphology, and variable involvement of other organ systems. Severely affected individuals with CDG-Ia usually present in the neonatal period with failure to thrive, developmental delay, abnormal subcutaneous fat distribution, elevated liver transaminases, and abnormal MRI findings. Later presenting individuals can have clinical features that include ataxia, significantly delayed motor and language development, seizures, stroke-like episodes, retinitis pigmentosa, joint contractures and skeletal deformities. An adult stable disability type has also been described. Currently, there is no cure and treatment remains primarily supportive and symptomatic.

 

Phosphomannose isomerase deficiency (MPI-CDG or CDG-Ib) is an autosomal recessive glycosylation disorder resulting from reduced or absent activity of phosphomannose isomerase, an enzyme encoded by the MPI gene. This CDG subtype is unique in that there is little to no involvement of the central nervous system. It is mainly hepatic-intestinal without dysmorphology, and the primary clinical manifestations are a result of aberrant gastrointestinal function. In particular, individuals with CDG-Ib may present with failure to thrive, hypoglycemia, chronic diarrhea, and protein-losing enteropathy. CDG-Ib is also unique in that it can be effectively treated with mannose supplementation, though it can be fatal if left untreated.

Interpretation

Normal results are not consistent with either phosphomannomutase-2 deficiency (PMM2-CDG or CDG-Ia) or phosphomannose isomerase deficiency (MPI-CDG or CDG-Ib).

 

Markedly reduced activity of phosphomannomutase is consistent with a diagnosis of CDG-Ia. Markedly reduced activity of phosphomannose isomerase is consistent with a diagnosis of CDG-Ib.

 

Mild to moderately reduced enzyme activities will be interpreted in the context of clinical and other laboratory test information submitted with the specimen.

Clinical Reference

1. Sparks SE, Krasnewich DM: Congenital Disorders of N-linked Glycosylation Pathway Overview. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle; Updated 2014 Jan 30. Available at www.ncbi.nlm.nih.gov/books/NBK1332/

2. Sparks SE, Krasnewich DM: PMM2-CDG (CDG-Ia) In GeneReviews. Edited by MP Adam, HH Ardinger, RA Pagon, et al. University of Washington, Seattle, Updated 2015 Oct 29. Available at www.ncbi.nlm.nih.gov/books/NBK1110/

3. Scott K, Gadomski T, Kozicz T, Morava E: Congenital disorders of glycosylation: new defects and still counting. J Inherit Metab Dis 2014 Jul;37(4):609-617

4. Jaeken J, Matthijs G, Carchon H, et al: Defects of N-Glycan Synthesis. In The Online Metabolic and Molecular Bases of Inherited Disease. 2014. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill, Accessed November 07, 2017. Available at www.ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62672837

Analytic Time

30-45 days

Method Name

Colorimetric

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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