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GM1 Gangliosidosis Workup

  • Author: David H Tegay, DO, FACMG; Chief Editor: Luis O Rohena, MD  more...
Updated: Dec 11, 2014

Laboratory Studies

Acid β -galactosidase activity: Diagnosis of G M1 gangliosidosis can be confirmed by measurement of acid β -galactosidase activity in peripheral blood leukocytes. Patients with the infantile form have almost no enzyme activity, whereas patients with the adult form may have residual activity of 5-10% of reference values. Overlap is often present between homozygotes without GM1 gangliosidosis and heterozygote carriers; therefore, screening for heterozygote carriers using enzyme analysis is not reliable.[1]

Urine: Galactose-containing oligosaccharides are excreted in the urine. Their presence may be used as an ancillary diagnostic test, and the concentration of the metabolites is proportional to disease severity.

CBC count: Vacuolation of lymphocytes may be present in patients with GM1 gangliosidosis but is a nonspecific indicator seen in a variety of lysosomal storage disorders.

Dried blood spots: Diagnosis of GM1 gangliosidosis has been made based on dried blood spots from newborn screening filter paper, even after 15 months in storage.[18]

Molecular analysis: Molecular analysis of the β -1 galactosidase gene (GLB1) is clinically available.[17, 2]


Imaging Studies

Radiography: Skeletal radiographs may reveal changes characteristic of dysostosis multiplex (as observed in mucopolysaccharidosis), including thickened calvaria, J-shaped enlarged sella turcica, wide spatula-shaped ribs, flared ilia, acetabular dysplasia and flat femoral heads, wide wedge-shaped metacarpals, shortened long bones with diaphyseal widening, and hypoplastic and anteriorly beaked thoracolumbar vertebrae. Delayed bone age also may be demonstrated. In the adult form, only mild vertebral changes may be observed.[1]

CT and MRI: Neuroimaging using CT scan or MRI generally reveals diffuse atrophy and white matter demyelination with or without basal ganglia changes. Bilateral T2-weighted hyperintensities in the putamen are a frequently reported MRI finding in adult-onset disease. Mild cerebral atrophy may also be observed in the adult form. MR spectroscopy has demonstrated increased striatal myoinositol.

Ultrasound: An ultrasound of the abdomen may reveal organomegaly.

Echocardiography: Signs of cardiomyopathy or valvulopathy may be observed.


Other Tests

Electrocardiography: Signs of cardiomyopathy may be observed.

Electroencephalography: This test may reveal generalized dysrhythmia and epileptogenic foci.



Acid β -galactosidase genotyping: Molecular diagnosis by direct sequencing can be useful for detecting heterozygous carriers and affected patients.[19, 17]

Lumbar puncture: GM1 ganglioside levels can be increased in the cerebrospinal fluid (CSF) and may be useful for diagnosis and monitoring.

Bone marrow aspiration: Do not use this procedure as a diagnostic test. Nonspecific large foam cells, Gaucher cells, and ballooned cells have been reported in bone marrow but are typically reported in lower concentrations than in other lysosomal storage disorders. Sea-blue histiocytes have been reported.[1]

Skin biopsy: Obtaining a skin biopsy may be useful to establish acid β -galactosidase activity in cultured fibroblasts.

Prenatal diagnosis: Prenatal diagnosis has been performed successfully by assay of β -galactosidase activity in cultured amniocytes or amniotic chorionic villi.[1] Mutation identification allows prenatal or preimplantation genetic diagnosis.


Histologic Findings

Cytoplasmic distention is observed diffusely within neurons and glial cells (with numerous membranous cytoplasmic bodies) because of accumulated GM1 ganglioside.

Neuronal number is decreased, and cortical architecture is distorted.

Extraneural lipid-laden histiocytes are observed in the liver, spleen, lymph nodes, thymus, lung, intestine, interlobular septa of the pancreas, and bone marrow. Their distended cytoplasm leads to eccentrically placed small pyknotic nuclei.[1]

Contributor Information and Disclosures

David H Tegay, DO, FACMG Associate Professor and Chair, Department of Medicine, NYIT College of Osteopathic Medicine; Director, Genetics Division, Department of Pediatrics, Nassau University Medical Center

David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American College of Osteopathic Internists, American Osteopathic Association, Federation of American Societies for Experimental Biology, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.


The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Shari Fallet, DO, to the original writing and development of this article.

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