Test Catalog

Test Id : GNPTZ

GNPTAB Gene, Full Gene Analysis, Varies

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

Molecular diagnosis or carrier status of mucolipidosis II alpha/beta and mucolipidosis III alpha/beta in conjunction with identification of characteristic clinical, radiographic, and biochemical findings, and genetic counseling for family members

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

Testing includes full gene sequencing of the GNPTAB gene.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

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

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

 

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions.

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

Polymerase Chain Reaction (PCR) Amplification/Universal Primer Sequencing of GNPTAB for all Coding Exons

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

GNPTAB Gene, Full Gene Analysis

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

Alpha and Beta Subunits

GNPTAB, N-Acetylglucosamine-1-Phosphate Transferase

GNPTAB-Related Mucolipidoses

I-Cell Disease

ML II Alpha/Beta

ML III Alpha/Beta

Mucolipidosis II Alpha/Beta

Mucolipidosis III Alpha/Beta

Pseudo-Hurler Polydystrophy

ML23S

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

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

 

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

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

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Specimen preferred to arrive within 96 hours of collection.

 

Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 flask or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

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. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

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

All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.

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
Varies Varies (preferred)

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

Molecular diagnosis or carrier status of mucolipidosis II alpha/beta and mucolipidosis III alpha/beta in conjunction with identification of characteristic clinical, radiographic, and biochemical findings, and genetic counseling for family members

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

Testing includes full gene sequencing of the GNPTAB gene.

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

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

 

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions.

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

N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits (GNPTAB)-related mucolipidoses are progressive lysosomal storage diseases traditionally classified as mucolipidosis II and mucolipidosis III based upon their severity and disease onset. These conditions have substantial clinical overlap and mutation testing can aid the diagnosis.

 

Mucolipidosis II alpha/beta (ML II alpha/beta or I-cell disease) is a progressive inborn error of metabolism with clinical onset at birth and fatal outcome most often in early childhood. Postnatal growth is limited and often ceases in the second year of life; contractures develop in all large joints. The skin is thickened, facial features are coarse, and gingiva are hypertrophic. Orthopedic abnormalities present at birth may include thoracic deformity, kyphosis, clubfeet, deformed long bones, and hip dislocation. There is often cardiac involvement, most commonly thickening and insufficiency of the mitral valve and, less frequently, the aortic valve. Progressive mucosal thickening narrows the airways and gradual stiffening of the thoracic cage contributes to respiratory insufficiency, the most common cause of death.

 

Mucolipidosis III alpha/beta (ML III alpha/beta or pseudo-Hurler polydystrophy) is a slowly progressive disorder with clinical onset at approximately 3 years of age. It is characterized by a slow growth rate and subnormal stature; radiographic evidence of mild-to-moderate dysostosis multiplex; joint stiffness and pain initially in the shoulders, hips, and fingers; gradual mild coarsening of facial features; and normal to mildly impaired cognitive development. If present, organomegaly is mild. Pain from osteoporosis that is clinically and radiologically apparent in childhood becomes more severe from adolescence. Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left and/or right ventricular hypertrophy) are common causes of death, typically in early to middle adulthood.

 

ML II/ML III alpha/beta are inherited in an autosomal recessive manner. Both disorders have been reported from nearly all parts of the world and the overall carrier rate ranges between 1 in 158 and 1 in 316.

 

GNPTAB is the gene in which mutations are most often known to cause ML II/ML III alpha/beta. Bidirectional sequencing of the entire GNPTAB coding region detects 2 disease-causing mutations in more than 95% of individuals with ML II/MLIII alpha/beta. This gene encodes 2 of 3 subunits (alpha/beta) of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. In the absence of this enzyme, a mannose 6-phosphate (M6P) recognition marker is not added to lysosomal hydrolases and other glycoproteins. This leads to disruption of acid hydrolases transport to the lysosome. Formation of the M6P recognition marker on lysosomal hydrolases is significantly reduced in ML III alpha/beta, and nearly or totally absent in ML II alpha/beta. 

 

To confirm or establish the diagnosis in a proband requires a combination of clinical evaluation and laboratory testing. The use of the following diagnostic testing is recommended: Identification of characteristic clinical and radiographic findings, assay of oligosaccharides in urine, assay of several acid hydrolases in plasma, sequence analysis of GNPTAB. The activity of nearly all lysosomal hydrolases in plasma and other body fluids is higher in individuals affected with ML II alpha/beta (5- to 20-fold) and ML III alpha/beta (up to 10-fold) than in normal controls. ML II/ML III alpha/beta is diagnosed by assay of N-acetylglucosamine-1-phosphotransferase in skin fibroblasts. Demonstration of nearly complete inactivity (<1%) of the enzyme confirms the diagnosis of ML II alpha/beta, whereas significant deficiency (1%-10% of normal) of this enzyme is suggestive of the diagnosis of ML III alpha/beta. Urinary excretion of oligosaccharides is often excessive. Prior to molecular analysis, the delineation of ML II alpha/beta from ML III alpha/beta depended solely on clinical criteria including age of onset, rate of progression, and overall severity.

 

Molecular genetic studies reveal a genotype-phenotype correlation supporting the clinical distinction between ML II alpha/beta and ML III alpha/beta. Mutations that completely inactivate the phosphotransferase consistently result in ML II alpha/beta, irrespective of their location within the gene. Mutations with less adverse effect on this enzyme activity usually result in ML III alpha/beta or occasionally in intermediate phenotypes.(1,2)

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.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

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

A small percentage of individuals who have a diagnosis of mucolipidoses II/III alpha/beta may have a mutation that is unidentifiable by this method (eg, large deletion/duplication, promoter mutations, deep intronic alterations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of mucolipidoses II/III alpha/beta. For carrier testing, it is important to first document the presence of GNPTAB mutations in an affected family member.

 

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

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

1. Kudo M, Brem MS, Canfield WM: Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene. Am J Hum Genet 2006;78:451-463

2. Cathey SS, Leroy JG, Wood T, et al: Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. J Med Genet 2010;47:38-48

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

A fluorescent DNA sequencing assay is used to detect sequence variants of GNPTAB on the ABI 3730x1 DNA Analyzer using universal sequencing primers.(Unpublished Mayo method)

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.

Performed weekly

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.

14 to 20 days

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.

81479-Unlisted molecular pathology procedure code

 

Fibroblast Culture for Genetic Test

 

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

 

88240-Cryopreservation (if appropriate)

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