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Test ID: GNPTZ GNPTAB Gene, Full Gene Analysis, Varies

Reporting Name

GNPTAB Gene, Full Gene Analysis

Useful For

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

Clinical Information

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)


An interpretive report will be provided.

Reflex Tests

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

Testing Algorithm

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.

Report Available

14 to 20 days

Day(s) Performed

Performed weekly

Clinical Reference

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

Method Name

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

Specimen Type


Specimen Required

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:



Specimen Type: Whole blood


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

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reference Values

An interpretive report will be provided.

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 US Food and Drug Administration.

CPT Code Information

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)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GNPTZ GNPTAB Gene, Full Gene Analysis 94201-1


Result ID Test Result Name Result LOINC Value
53484 Result Summary 50397-9
53485 Result 82939-0
53486 Interpretation 69047-9
53487 Additional Information 48767-8
53488 Specimen 31208-2
53489 Source 31208-2
53490 Released By 18771-6


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