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

Glycogen-Storage Disease Type II: Differential Diagnoses & Workup

Author: Jennifer Ibrahim, MD, Chief, Genetics Division, St Joseph's Children's Hospital
Coauthor(s): Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Contributor Information and Disclosures

Updated: Oct 7, 2009

Differential Diagnoses

Cardiomyopathy, Hypertrophic
Endocardial Fibroelastosis
Limb-Girdle Muscular Dystrophy
Metabolic Myopathies

Other Problems to Be Considered

Organic acidurias
Mitochondrial disorders

Workup

Laboratory Studies

The following studies are indicated in glycogen-storage disease type II (GSDII)

  • Serum creatine kinase (CK)
    • General reflection of muscle disease
    • Greatest elevation among infants with glycogen-storage disease type II
    • As much as 10 times normal level
  • Serum aspartate aminotransferase
    • Highest among infants with glycogen-storage disease type II
    • Reflects liver involvement
  • Enzyme activity
    • Definitive diagnosis requires the measurement of acid alpha-glucosidase activity in cultured skin fibroblasts or peripheral blood lymphocytes. Testing in lymphocytes usually requires 10 mL of whole blood in heparinized tubes, from which a white cell pellet is generated. This may not be practical in an infant. A mixed leukocyte analysis may lead to errors because granulocytes also contain a renal isomer of acid maltase, which is active in an acidic pH.
    • Reliable diagnosis can be made from a dried blood spot, such as collected for state newborn screening tests. Pilot programs for newborn detection of Pompe disease are anticipated in the near future.
    • A muscle biopsy can help establish a diagnosis but is unnecessarily invasive.
    • Clinical analysis of GAA is available. However, the assay may fail to reveal both mutations in an affected individual. Therefore, DNA testing cannot be used in place of enzyme assay to establish the diagnosis. DNA analysis can be helpful in the identification of carriers in a family with an affected individual.

Imaging Studies

  • Echocardiography establishes the degree of cardiac involvement and may also allow one to distinguish between the infantile and juvenile forms of glycogen-storage disease type II. It may show overall enlargement of the heart, isolated left ventricle (LV) thickening, biventricular thickening, or outflow obstruction in advanced disease.

Other Tests

  • ECG
    • This test also establishes the presence and degree of cardiac involvement.
    • The characteristic finding is shortening of the PR interval.
    • Enlargement of the QRS complex also may occur.
  • Electromyography
    • The electromyography (EMG) of all patients reveals a myopathic pattern.
    • Many patients exhibit pseudomyotonic discharges (ie, myotonic discharges in the absence of clinical myotonia), fibrillation potentials, and positive waves due to the anterior horn cell involvement.

Procedures

  • Skin biopsy findings reveal acid alpha-glucosidase activity in cultured fibroblasts.

Histologic Findings

  • Light microscopy reveals large glycogen-containing vacuoles in nearly all muscle fibers.
  • These vacuoles can be further characterized histochemically as secondary lysosomes. In general, type I and type II muscle fibers are equally affected.
  • Electron microscopy is used to classify subtypes of the vacuoles in which glycogen accumulates.
  • Histopathological examination of muscle is not necessary to establish diagnosis.

More on Glycogen-Storage Disease Type II

Overview: Glycogen-Storage Disease Type II
Differential Diagnoses & Workup: Glycogen-Storage Disease Type II
Treatment & Medication: Glycogen-Storage Disease Type II
Follow-up: Glycogen-Storage Disease Type II
Multimedia: Glycogen-Storage Disease Type II
References
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References

  1. Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet. Sep 1999;7(6):713-6. [Medline].

  2. Miyamoto Y, Etoh Y, Joh R, et al. Adult-onset acid maltase deficiency in siblings. Acta Pathol Jpn. Nov 1985;35(6):1533-42. [Medline].

  3. Bulkley BH, Hutchins GM. Pompe's disease presenting as hypertrophic myocardiopathy with Wolff-Parkinson-White syndrome. Am Heart J. Aug 1978;96(2):246-52. [Medline].

  4. Kroos MA, Pomponio RJ, Hagemans ML, et al. Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype. Neurology. Jan 9 2007;68(2):110-5. [Medline].

  5. van der Beek NA, Soliman OI, van Capelle CI, Geleijnse ML, Vletter WB, Kroos MA, et al. Cardiac evaluation in children and adults with Pompe disease sharing the common c.-32-13T>G genotype rarely reveals abnormalities. J Neurol Sci. Dec 15 2008;275(1-2):46-50. [Medline].

  6. Kishnani PS, Corzo D, Leslie ND, et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res. Sep 2009;66(3):329-35. [Medline].

  7. Nicolino M, Byrne B, Wraith JE, et al. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med. Mar 2009;11(3):210-9. [Medline].

  8. Merk T, Wibmer T, Schumann C, Krüger S. Glycogen storage disease type II (Pompe disease)--influence of enzyme replacement therapy in adults. Eur J Neurol. Feb 2009;16(2):274-7. [Medline].

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  10. Ausems MG, Lochman P, van Diggelen OP, et al. A diagnostic protocol for adult-onset glycogen storage disease type II. Neurology. Mar 10 1999;52(4):851-3. [Medline].

  11. Clinical Trials. A Study to Evaluate the Effects of Pharmacological Chaperones in Cells From Patients With Pompe Disease. clinicaltrials.gov. Available at http://clinicaltrials.gov/ct/show/NCT00515398?order=2. Accessed 2007.

  12. Engel AG, Gomez MR, Seybold ME, Lambert EH. The spectrum and diagnosis of acid maltase deficiency. Neurology. Jan 1973;23(1):95-106. [Medline].

  13. Engel AG, Hirschhorn R. Acid maltase deficiency. In: Engel AG, Franzine-Armstrong C, eds. Myology: Basic and Clinical. New York, NY: McGraw-Hill; 1996:1533-53.

  14. Hirschhorn R. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Sly W, Valle E, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 1995:2443-64.

  15. Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL,et, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. 2001;3389-3420.

  16. Isaacs H, Savage N, Badenhorst M, Whistler T. Acid maltase deficiency: a case study and review of the pathophysiological changes and proposed therapeutic measures. J Neurol Neurosurg Psychiatry. Sep 1986;49(9):1011-8. [Medline].

  17. Umapathysivam K, Hopwood JJ, Meikle PJ. Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease. Clin Chem. Aug 2001;47(8):1378-83. [Medline].

  18. Van der Beek NA, Hagemans ML, Reuser AJ, Hop WC, Van der Ploeg AT, Van Doorn PA, et al. Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease. Neuromuscul Disord. Feb 2009;19(2):113-7. [Medline].

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Further Reading

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Keywords

GSDII, Pompe disease, Pompe's disease, acid maltase deficiency, AMD, alpha-1, 4 glucosidase deficiency, glucosidase acid alpha deficiency, GAA deficiency, cardiac form of generalized glycogenosis, glycogen-storage disease type II, type 2 glycogenosis, idiopathic hypertrophic cardiomyopathy, hypoglycemia, cardiomegaly, basilar artery aneurysm, sleep apnea, hypotonia, Wolff-Parkinson-White syndrome, macroglossia, hepatomegaly, enlargement of the heart, isolated left ventricle thickening, biventricular thickening, outflow obstruction, treatment, diagnosis

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Contributor Information and Disclosures

Author

Jennifer Ibrahim, MD, Chief, Genetics Division, St Joseph's Children's Hospital
Jennifer Ibrahim, MD is a member of the following medical societies: American Society of Human Genetics
Disclosure: Nothing to disclose.

Coauthor(s)

Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Genzyme Grant/research funds PI

Medical Editor

Edward Kaye, MD, Vice President of Clinical Research, Genzyme Corporation
Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders
Disclosure: Genzyme Corporation Salary Management position

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

Hagop Youssoufian, MD, MSc, Vice President of Clinical Research, ImClone Systems Incorporated
Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human 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, 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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