eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

GM1 Gangliosidosis: Differential Diagnoses & Workup

Author: David H Tegay, DO, FACMG, Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center
Contributor Information and Disclosures

Updated: Jun 8, 2009

Differential Diagnoses

GM2 Gangliosidoses
I-Cell Disease (Mucolipidosis Type II)
Mucopolysaccharidosis Type IH
Mucopolysaccharidosis Type IV
Sialidosis (Mucolipidosis I)
Wilson Disease

Other Problems to Be Considered

Galactosialidosis (combined a -neuraminidase and b -galactosidase deficiency)
Oligosaccharidosis (eg, mannosidosis, fucosidosis, sialidosis)
Parkinson disease
Isolated dystonia

Workup

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.11
  • Molecular analysis: Molecular analysis of the β -1 galactosidase gene (GLB1) is clinically available.10,2

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.

Procedures

  • Acid b -galactosidase genotyping: Molecular diagnosis by direct sequencing can be useful for detecting heterozygous carriers and affected patients.12,10
  • 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 b -galactosidase activity in cultured fibroblasts.
  • Prenatal diagnosis: Prenatal diagnosis has been performed successfully by assay of b -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

More on GM1 Gangliosidosis

Overview: GM1 Gangliosidosis
Differential Diagnoses & Workup: GM1 Gangliosidosis
Treatment & Medication: GM1 Gangliosidosis
Follow-up: GM1 Gangliosidosis
References
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References

  1. Suzuki Y, Oshima A, Nanba E. B-Galactosidase deficiency (B-Galactosidosis): GM1 gangliosidosis and Morquio B disease. In: Scriver CR, Sly WS, Valle D, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill Professional; 2001:3775-810.

  2. Brunetti-Pierri N, Scaglia F. GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab. Aug 2008;94(4):391-6. [Medline].

  3. Suzuki K. Neuropathology of late onset gangliosidoses. A review. Dev Neurosci. 1991;13(4-5):205-10. [Medline].

  4. Muthane U, Chickabasaviah Y, Kaneski C, et al. Clinical features of adult GM1 gangliosidosis: report of three Indian patients and review of 40 cases. Mov Disord. Nov 2004;19(11):1334-41. [Medline].

  5. Roze E, Paschke E, Lopez N, et al. Dystonia and parkinsonism in GM1 type 3 gangliosidosis. Mov Disord. Oct 2005;20(10):1366-9. [Medline].

  6. Lenicker HM, Vassallo Agius P, Young EP, Attard Montalto SP. Infantile generalized GM1 gangliosidosis: high incidence in the Maltese Islands. J Inherit Metab Dis. Sep 1997;20(5):723-4. [Medline].

  7. Severini MH, Silva CD, Sopelsa A, et al. High frequency of type 1 GM1 gangliosidosis in southern Brazil. Clin Genet. Aug 1999;56(2):168-9. [Medline].

  8. Hanson M, Lupski JR, Hicks J, Metry D. Association of dermal melanocytosis with lysosomal storage disease: clinical features and hypotheses regarding pathogenesis. Arch Dermatol. Jul 2003;139(7):916-20. [Medline].

  9. Snow TM. Mongolian spots in the newborn: do they mean anything?. Neonatal Netw. Jan-Feb 2005;24(1):31-3. [Medline].

  10. Suzuki Y, Sakuraba H, Oshima A, et al. Clinical and molecular heterogeneity in hereditary beta-galactosidase deficiency. Dev Neurosci. 1991;13(4-5):299-303. [Medline].

  11. Chamoles NA, Blanco MB, Iorcansky S, et al. Retrospective diagnosis of GM1 gangliosidosis by use of a newborn-screening card. Clin Chem. Nov 2001;47(11):2068. [Medline]. [Full Text].

  12. Morrone A, Bardelli T, Donati MA, et al. Beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement. Hum Mutat. 2000;15(4):354-66. [Medline].

  13. Shield JP, Stone J, Steward CG. Bone marrow transplantation correcting beta-galactosidase activity does not influence neurological outcome in juvenile GM1-gangliosidosis. J Inherit Metab Dis. 2005;28(5):797-8. [Medline].

  14. Wynn RF, Wraith JE, Mercer J, et al. Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy. J Pediatr. Apr 2009;154(4):609-11. [Medline].

  15. [Guideline] Cunningham M, Cox EO. Hearing assessment in infants and children: recommendations beyond neonatal screening. Pediatrics. Feb 2003;111(2):436-40. [Medline].

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Further Reading

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Keywords

GM1 gangliosidosis, acid beta-galactosidase-1 deficiency, GLB1 deficiency, Morquio disease type B, Norman-Landing disease, Landing disease, lysosomal storage disorder, ganglioside accumulation, oligosaccharide accumulation, mucopolysaccharide accumulation, keratan sulfate, dementia, coarse facial features, hepatosplenomegaly, generalized skeletal dysplasia, macular cherry-red spots, scoliosis, treatment, diagnosis

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Contributor Information and Disclosures

Author

David H Tegay, DO, FACMG, Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center
David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Human Genetics, and Federation of American Societies for Experimental Biology
Disclosure: Nothing to disclose.

Medical Editor

Ian Krantz, MD, Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia
Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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 and American College of Medical Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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