Test Catalog

Test Id : PMMIL

Phosphomannomutase and Phosphomannose Isomerase, Leukocytes

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

 

This test is not useful for carrier testing.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Congenital disorders of glycosylation (CDG) are a large and growing group of inborn errors of glycan metabolism that are clinically diverse, but most often present during infancy or childhood.

 

A diagnostic workup for a CDG should begin with transferrin analysis by liquid chromatography-mass spectrometry (CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum).

 

Follow-up testing of an abnormal transferrin isoform profile may include enzymatic analysis for the diagnosis of phosphomannomutase-2 deficiency (PMM2-CDG or CDG-Ia) and phosphomannose isomerase deficiency (MPI-CDG or CDG-Ib).

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Colorimetric

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

PMM-PMI, Leukocytes

Aliases
Lists additional common names for a test, as an aid in searching

CDG (Congenital Disorders of Glycosylation)Type I

CDG-Ia

CDG-Ib

Congenital Disorders of Glycosylation (CDG)Type I

Phosphomannose Isomerase (PMI)

PMM (Phosphomannomutase)

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Specimen Type
Describes the specimen type validated for testing

Whole Blood ACD

Ordering Guidance

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.

Shipping Instructions

For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerated within 6 days of collection to be stabilized. Collect specimen Monday through Thursday only and not the day before a holiday. Specimen should be collected and packaged as close to shipping time as possible.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A)

Specimen Volume: 6 mL

Collection Instructions: Send specimen in original tube. Do not aliquot.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

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

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

3 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole Blood ACD Refrigerated (preferred) 6 days YELLOW TOP/ACD
Ambient 6 days YELLOW TOP/ACD

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

 

This test is not useful for carrier testing.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Congenital disorders of glycosylation (CDG) are a large and growing group of inborn errors of glycan metabolism that are clinically diverse, but most often present during infancy or childhood.

 

A diagnostic workup for a CDG should begin with transferrin analysis by liquid chromatography-mass spectrometry (CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum).

 

Follow-up testing of an abnormal transferrin isoform profile may include enzymatic analysis for the diagnosis of phosphomannomutase-2 deficiency (PMM2-CDG or CDG-Ia) and phosphomannose isomerase deficiency (MPI-CDG or CDG-Ib).

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Congenital disorders of glycosylation (CDG) are a group of over 100 inherited metabolic disorders largely affecting N- and O-glycosylation of proteins. CDG typically present as multisystemic disorders and may include developmental delay, hypotonia, abnormal magnetic resonance imaging 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 such as phosphomannose isomerase (MPI)-CDG (CDG-Ib) 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 with phenotypic variability ranging from severely affected infants to mildly affected adults. In infancy, patients with CDG-Ia will typically present with neurological involvement such as axial hypotonia, hyporeflexia, developmental delay, cerebellar hypoplasia, failure to thrive, hepatopathy, and abnormal subcutaneous fat distribution. There is variable involvement of other organ systems including features such as heart defects, epilepsy, strabismus, retinitis pigmentosa, liver dysfunction, endocrine abnormalities such as hypothyroidism and hypoglycemia, and skeletal deformities. 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 can be fatal if left untreated.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

PHOSPHOMANNOMUTASE

Normal >350 nmol/h/mg protein

 

PHOSPHOMANNOSE ISOMERASE

Normal >1,300 nmol/h/mg protein

Interpretation
Provides information to assist in interpretation of the test results

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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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). However, white blood cell enzyme activity is still more reliable than fibroblast testing for PMM2-CDG.(1,2) The PMM2 enzyme result should be considered along with CDG transferrin, clinical phenotype, and genotype when determining a diagnosis.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Grunewald S, Schollen E, Van Schaftingen E, Jaeken J, Matthijs G: High residual activity of PMM2 in patients' fibroblasts: possible pitfall in the diagnosis of CDG-Ia (phosphomannomutase deficiency). Am J Hum Genet. 2001 Feb;68(2):347-354

2. Pirard M, Matthijs G, Heykants L, et al: Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2. FEBS Lett. 1999 Jun 11;452(3):319-322

3. Lam C, Krasnewich DM: PMM2-CDG. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2005. Updated May 20, 2021 Accessed August 12, 2021. Available at: www.ncbi.nlm.nih.gov/books/NBK1110/

4. Schiff M, Roda C, Monin ML, et al: Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature. J Med Genet. 2017 Dec;54(12):843-851

5. Girard M, Douillard C, Debray D, et al: Long term outcome of MPI-CDG patients on D-mannose therapy. J Inherit Metab Dis. 2020 Nov;43(6):1360-1369

6. Jaeken J, Matthijs G, Carchon H, Van Schaftingen E: Defects of N-glycan synthesis. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed July 20, 2021. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225081470

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Preanalytical processing: Monday through Saturday

Assay performed: Twice per month

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

30 to 45 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

WBC homogenate: 1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82657

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PMMIL PMM-PMI, Leukocytes 100735-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
50842 Phosphomannomutase, Leuko 78970-1
50843 Phosphomannose Isomerase, Leuko 78963-6
50840 Reason For Referral 42349-1
50836 Specimen 31208-2
50837 Specimen ID 57723-9
50838 Source 31208-2
50839 Order Date 82785-7
50841 Method 85069-3
50845 Amendment 48767-8
50847 Release Date 82772-5
50844 Interpretation 59462-2
50846 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports