GM1 Diagnostic Testing Guide

FAMILY RESOURCE SERIES Version 1 · July 2026

GM1 Diagnostic Testing Guide

In This Article

Introduction: GM1 Testing Types

GM1 gangliosidosis is a rare, inherited lysosomal storage disease caused by mutations in the GLB1 gene, which encodes the enzyme beta-galactosidase (beta-gal). Genetic changes, called variants (mutations), in both copies of the GLB1 gene can prevent the enzyme from working properly. This leads to a toxic buildup of GM1 ganglioside, a harmful substance that primarily affects the brain and nervous system. The disease spans a broad spectrum: severe infantile forms (Type 1) with onset in the first months of life; juvenile (Type 2) and adult-onset (Type 3) forms. [1][2]

[Note: Mucopolysaccharidosis type IVB (Morquio type B syndrome) is a milder skeletal condition caused by the same gene though not further reviewed here.][3]

There are two complementary types of laboratory testing which may be used to diagnose GM1, confirm carrier status, or guide family planning:

  • Beta-galactosidase enzyme activity testing – a biochemical assay that measures how much functional enzyme is present in blood or skin cells.
  • GLB1 gene sequencing – a molecular genetic test that identifies the changes in GLB1 that may be causative of GM1.

Both test types are available through CLIA-certified laboratories in the United States as well as labs around the world with country-specific regulations. Testing may be ordered by metabolic or biochemical geneticists, medical geneticists, pediatric or adult neurologists, primary care physicians, or genetic counselors. This guide covers what each test does, reasons to order it, how to access it, and which laboratories and specialists can help.

Part i: Beta-Galactosidase Enzyme Activity Testing

What Is This Test?

The beta-galactosidase enzyme assay measures the activity level of the beta-gal enzyme in a patient’s cells. It is the first-tier diagnostic test for GM1 gangliosidosis.[1]

  • Markedly reduced or absent enzyme activity confirms the diagnosis of GM1 gangliosidosis.
  • Activity levels help classify disease severity: lower activity correlates with more severe disease (Type 1); residual activity with milder phenotypes (Types 2 and 3), however, it is difficult to provide an accurate correlation between enzyme activity and disease severity.[2][4]

What Samples Are Used for This Test?

  • Whole blood (leukocyte cells)
  • Dried blood spots 
  • Cultured fibroblasts* (skin punch biopsy sent for a cell culture)

*Requires special handling and should be ordered through a knowledgeable healthcare provider

When to Order This Test?

Beta-galactosidase enzyme testing may be ordered for a suspected or clinical diagnosis of GM1. Clinical indications may include:

  • Unexplained neurological regression, progressive developmental delay, or loss of motor skills
  • Clinical findings or skeletal abnormalities suggestive of lysosomal storage disease
  • Biochemical test results suspicious for GM1 including an oligosaccharide profile consistent with GM1 
  • Family history of GM1 gangliosidosis (affected sibling or close relative)
  • Abnormal newborn screening result suggestive of GM1
  • GLB1 variant of uncertain significance (VUS) 

Part II: GLB1 Gene Sequencing

What Is This Test?

While enzyme activity testing tells you how much enzyme is present, GLB1 genetic testing reveals why by identifying the exact genetic or DNA changes that cause the enzyme deficiency. Genetic testing uses gene sequencing to look for single base changes, small insertions/deletions, large exon-level deletions/duplications, or genetic rearrangements.  Genetic testing is essential for:

  • Confirming the genetic diagnosis 
  • Correlating genotype with clinical signs or symptoms to understand likely disease course
  • Supporting clinical trial enrollment – most trials require a confirmed genetic diagnosis
  • Carrier testing for parents, siblings, and extended family members
  • Reproductive planning, including prenatal diagnosis and preimplantation genetic testing (PGT-M)[5]

What Samples Are Used for This Test?

  • Whole blood (leukocyte cells)
  • Dried blood spots 
  • Oral swabs, including buccal (cheek) and saliva
  • Cultured fibroblasts* (skin punch biopsy sent for a cell culture, rarely used for gene sequencing)

When to Order This Test?

GLB1 gene sequencing may be ordered for a suspected or clinical diagnosis of GM1. Clinical indications may include:

  • Unexplained neurological regression, progressive developmental delay, or loss of motor skills
  • Clinical findings or skeletal abnormalities suggestive of lysosomal storage disease
  • Beta-galactosidase enzyme deficiency
  • Abnormal newborn screening result suggestive of GM1
  • Family history of GM1 gangliosidosis (affected sibling or close relative)

What types of genetic testing exist?

GLB1 Single Gene Sequencing

  • What it detects: Analyzes the coding regions of the GLB1 gene
  • Best used when: Primary test when enzyme activity is low and clinical suspicion is clear

Multi-Gene Panel (many types)

  • What it detects: Sequences the coding regions of 10’s to 100’s of genes that are known to be related to a group of conditions or symptoms at the same time
  • Best used when: When diagnosis is uncertain and other lysosomal conditions are possible

Exome Sequencing

  • What it detects: Analyzes the coding regions of all genes in the genome 
  • Best used when: When diagnosis is uncertain and other non-lysosomal conditions are possible

Genome Sequencing

  • What it detects: Analyzes the coding and non-coding regions of all genes in the genome 
  • Best used when: When prior genetic testing is non-diagnostic

Test type: Targeted Familial Variant Testing

  • What it detects: Tests only for the specific GLB1 variant(s) already identified in the family
  • Best used when: For carrier testing of family members once variants are known in a person with GM1

Important collection Notes

Always confirm shipping requirements with the lab before collecting a sample. Ship Monday through Thursday to avoid weekend transit delays, and check with the laboratory for holiday closures. For patients who reside in the state of New York, verify a current permit is in place to order testing performed by a non-New York laboratory.

Testing Laboratories (listed here for relevance to GM1)

Laboratories offering both biochemical and genetic testing

Greenwood Genetics Center – SC

  • Website: https://ggc.org/providers/diagnostic-lab/ 
  • Enzyme Tests:
    • Beta-galactosidase Enzyme Analysis (Test code BBGLL, BBGLF, BBGLD)
    • Lysosomal Storage Disease Enzyme Panel (leukocytes, Test code BLSB)
    • Lysosomal Storage Disease Enzyme Panel (DBS) (Test code BLED)
  • Genetic Tests:
    • GLB1 Sequencing (Test code DGLB)
  • Sample Requirements: Refer to each test link
  • Email:  labsupport@ggc.org
  • Phone: 1-800-473-9411

Lysosomal Diseases Testing Laboratory (LDTL) – Thomas Jefferson University – PA

Mayo Clinic Laboratories – Minnesota

  • Website: https://www.mayocliniclabs.com/ 
  • Enzyme Tests:
    • Beta-Galactosidase (Leukocytes; Test code BGA)
    • Mucopolysaccharidosis IV Enzyme Panel (Leukocytes; Test code MPS4W)
    • Mucopolysaccharidosis IV Enzyme Panel (Blood Spot; Test code MPS4B)
  • Genetic Tests:
    • GLB1 Single Gene Sequencing (Custom Gene Panel, Test code CGPH, GLB1 Gene List ID: IEMCP-D5F3YS)
    • Lysosomal Storage Disease Gene Panel (Test code LSDGP)
  • Sample Requirements: Refer to each test link
  • Email:  mcl@mayo.edu
  • Phone: 800-533-1710

The Hospital for Sick Children – Rapid Response Laboratory – Toronto, Canada

Laboratories offering genetic testing

Fulgent – CA

  • Website: https://fulgentgenetics.com/
  • Enzyme Tests: N/A
  • Genetic Tests:
    • Mucopolysaccharidosis NGS Panel (Link)
  • Sample Requirements: Link
  • Email:  info@fulgentgenetics.com
  • Phone: (626) 350-0537

Labcorp | Invitae – CA

  • Website: https://www.invitae.com/ 
  • Enzyme Tests: N/A
  • Genetic Tests: SEVERAL
    • Invitae Comprehensive Lysosomal Storage Disorders Panel (Test code: 06170)
    • Invitae Neurodevelopmental Disorders (NDD) Panel (Test code: 728434)
  • Sample Requirements:  Link
  • Email:  clientservices@invitae.com
  • Phone: 800-436-3037

PreventionGenetics – WI

  • Website: https://www.preventiongenetics.com/ 
  • Enzyme Tests: N/A
  • Genetic Tests:
    • Lysosomal Storage Disorders Panel (Test code: 13065; Link)
  • Sample Requirements: Link
  • Email:  support@preventiongenetics.com
  • Phone: 715-387-0484 

Other laboratories with large panels, exome, or genome sequencing for diagnostic screening that may include the GLB1 gene are also available through the following labs: Ambry (https://www.ambrygen.com/providers/neurology/test-menu), GeneDx (https://www.genedx.com/), Natera (https://www.natera.com/rare-disease/zenith/).

Some laboratories offer no-charge, sponsored genetic testing programs through which the costs of testing may be paid by external companies. Information about relevant programs can be found on the laboratory websites below: 

Broad US and international laboratory directories are available using the following resources:

  • Genetic Testing Registry (Link)
  • Orphanet rare disease directory (Link)

Part III – Finding a Specialist

Interpreting results, diagnosing, and managing care for GM1 gangliosidosis requires a specialist with expertise in lysosomal storage disorders. The following centers have active clinical programs or published research in GM1:

GM1 Diagnostic Testing Institutions

To find a genetic counselor near you, visit the National Society of Genetic Counselors https://findageneticcounselor.nsgc.org/ 

Part IV: Cost, Insurance and Financial Assistance

Beta-galactosidase Enzyme Testing 

Covered by most major commercial insurance plans and Medicaid when ordered with appropriate clinical indication. The CPT code for enzyme testing is 82657 which may be requested for prior authorization.

GLB1 Genetic Testing 

Coverage varies by plan. Many insurers cover single gene, multi-gene panel and exome/genome testing when there is documented clinical suspicion. Many CPT codes are used and can be provided by the laboratory for a test of interest when requested to determine prior authorization.

Some insurers may require prior authorization. If denied, a written appeal with a clinical letter of necessity from a geneticist is often effective.

Prior Authorization Tips

Encourage your healthcare provider to request a prior authorization before the test is ordered. Include documentation of symptoms, family history, and supporting medical literature in the authorization request. The ICD-10 diagnosis code for GM1 gangliosidosis is E75.19.

Financial Hardship Options

Most major genetic testing laboratories (Ambry Genetics, GeneDx, Labcorp|Invitae, PreventionGenetics) have dedicated financial assistance teams that can discuss rates for uninsured or underinsured patients. 

  • Always call the laboratory before assuming a test is unaffordable – options almost always exist.

About Cure GM1 Foundation

Cure GM1 Foundation is a nonprofit organization founded by families living with GM1 gangliosidosis. Our mission is to accelerate the development of effective treatments by funding research, supporting families, and advocating for improved diagnostic access and care standards. 

This document is published as a public educational resource and should not be used to diagnose or treat any health condition. Please consult a medical professional for questions about diagnosis and management. For questions, corrections, or updated information, contact us at info@curegm1.org or visit curegm1.org.

The Research Behind This Guide

This summary is based on nine published studies. If you would like to read them or share them with your medical team, they are listed here:

1. Regier DS, Tifft CJ, Rothermel CE. GLB1-Related Disorders. In: GeneReviews® [Internet]. Seattle (WA): University of Washington; 2013 Oct 17 [updated 2021]. PMID: 24156116. https://www.ncbi.nlm.nih.gov/books/NBK164500/

2. Arash-Kaps L, Komlosi K, Seegräber M, et al. The Clinical and Molecular Spectrum of GM1 Gangliosidosis. J Pediatr. 2019;215:152-157.e3. doi:10.1016/j.jpeds.2019.08.016. https://doi.org/10.1016/j.jpeds.2019.08.016

3. Caciotti A, Tonin R, Mort M, et al. Morquio B disease: From pathophysiology towards diagnosis. Mol Genet Metab. 2021;132(2):66-77. doi:10.1016/j.ymgme.2021.01.008. https://doi.org/10.1016/j.ymgme.2021.01.008

4. Lewis S, Fischer M, Rankin J, et al. Retrospective assessment of clinical global impression of severity and change in GM1 gangliosidosis: a tool to score natural history data in rare disease cohorts. Orphanet J Rare Dis. 2025;20(1):119. doi:10.1186/s13023-025-03614-6. https://doi.org/10.1186/s13023-025-03614-6

5. Zagaynova E, et al. Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis. Front Genet. 2024;15:1344051. doi:10.3389/fgene.2024.1344051. https://doi.org/10.3389/fgene.2024.1344051

Frequently Asked Questions

The beta-galactosidase enzyme activity assay is the first-tier diagnostic test. Markedly reduced or absent enzyme activity confirms a diagnosis of GM1 gangliosidosis, and activity levels can help indicate disease severity.

Enzyme testing measures how much functional beta-gal enzyme is present in a patient’s cells, while GLB1 gene sequencing identifies the exact genetic changes causing the enzyme deficiency. The two tests are complementary and are often used together to confirm a diagnosis, guide family planning, or support clinical trial enrollment.

Both enzyme and genetic testing can use whole blood or dried blood spots. Genetic testing can also use oral swabs (buccal/saliva), and both test types may use cultured fibroblasts from a skin punch biopsy, though that requires special handling.

Beta-galactosidase enzyme testing (CPT code 82657) is covered by most major commercial insurance plans and Medicaid when ordered with appropriate clinical indication. Coverage for GLB1 genetic testing varies by plan, and some insurers may require prior authorization.

Testing may be ordered by metabolic or biochemical geneticists, medical geneticists, pediatric or adult neurologists, primary care physicians, or genetic counselors.

Prepared by the CureGM1 Foundation. For more information: curegm1.org | info@curegm1.org

This document does not constitute medical advice. Always discuss treatment decisions with your child’s medical team.