Acid Maltase Deficiency Myopathy Workup

  • Author: Michael Weinik, DO; Chief Editor: Denise I Campagnolo, MD, MS   more...
 
Updated: Jan 18, 2012
 

Laboratory Studies

  • Serum CK usually is elevated in the forms of the disease that affect younger patients, but CK can be within the reference range in the adult variety. CK levels can be as high as 2000 IU/L.
  • Serum aspartate aminotransferase and lactic dehydrogenase can also be elevated.
  • The tissue concentration level of acid maltase helps to establish a definite diagnosis.[12]
Next

Imaging Studies

  • In patients with acid maltase deficiency, chest radiographs reveal an enlarged, globular heart associated with pulmonary vascular congestion. Atelectasis can also be seen.
Previous
Next

Other Tests

  • EMG
    • Brief, small-amplitude, polyphasic potentials or myopathic features, excessive electrical irritability, and pseudomyotonic discharges usually are seen on EMG.
    • A myopathy is demonstrated.
    • Neuropathic findings may be revealed.
    • Pseudomyotonia may be seen in the absence of myotonia.
  • Electrocardiographic findings include extremely tall and broad QRS complexes (representing ventricular depolarization) with a short PR interval (time between P wave and the beginning of the QRS complex), commonly less than 0.009 seconds. The short PR interval may be due to facilitated atrioventricular conduction as a result of myocardial glycogen deposition. A distinct left ventricular trabeculation can be seen on selective angiography.
  • Prenatal/postnatal testing
    • Prenatal diagnosis using chorionic villi or amniocentesis is available for the fatal infantile form. Decreased serum levels of acid maltase can be detected. Acid phosphatase levels also can be measured and will be elevated.
    • Newborn screening for Pompe disease can be performed by determining the total acid alpha-glucosidase in plasma or dried blood spots. The sensitivity of these tests is 82-95%, and the specificity is 100%.
Previous
Next

Procedures

  • Biopsy
    • The diagnosis of acid maltase deficiency (AMD) usually is made based on the absence or reduction in the levels of alpha-acid maltase in muscle tissue or cultured skin fibroblasts. This deficiency usually is more pronounced in the infantile form than in the juvenile and adult forms.
    • Muscle biopsy shows the presence of vacuoles that stain positive for glycogen. The large vacuoles contain material that is positive for the periodic acid-Schiff stain (typical of lysosomal glycogen storage). Acid phosphatase is increased, most likely because of a compensatory increase in the production of lysosomal enzymes. Electron microscopy reveals glycogen accumulation within the vacuoles and in the cytoplasm.
    • Brain tissue samples from patients with AMD reveal swelling of the perinuclear space (perikaryal edema) caused by excessive storage of glycogen. These cells usually display absence or dispersion of Nissl substance. The cytoplasm may be foamy or stained irregularly, and the nucleus may not be displaced to the periphery. Storage-induced changes tend to be more diffuse or multifocal rather than localized.
Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Michael Weinik, DO  Associate Chairman, Associate Professor, Physical Medicine and Rehabilitation, Temple University Hospital

Michael Weinik, DO is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Coauthor(s)

Frank J King, MD  Clinical Instructor, Department of Physical Medicine and Rehabilitation, Georgia Pain Physicians/Emory School of Medicine

Frank J King, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, and Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Specialty Editor Board

Elizabeth A Moberg-Wolff, MD  Medical Director, Pediatric Rehabilitation Medicine Associates

Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation

Disclosure: Medtronic Neurological None Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Kat Kolaski, MD  Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine

Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Kelly L Allen, MD  Medical Director, Medevals

Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS  Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers

Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers

Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching; Genzyme Corporation Grant/research funds investigator; Biogen Idec Grant/research funds investigator; Genentech, Inc Grant/research funds investigator; Eli Lilly & Company Grant/research funds investigator; Novartis investigator; MSDx LLC Grant/research funds investigator; BioMS Technology Corp Grant/research funds investigator; Avanir Pharmaceuticals Grant/research funds investigator

Additional Contributors

The editors would like to thank Daniel A Lee, MD, for his previous association with this article.

References

  1. Fukuda T, Roberts A, Plotz PH, et al. Acid alpha-glucosidase deficiency (Pompe disease). Curr Neurol Neurosci Rep. Jan 2007;7(1):71-7. [Medline].

  2. van der Ploeg AT, Reuser AJ. Pompe's disease. Lancet. Oct 11 2008;372(9646):1342-53. [Medline].

  3. Bembi B, Cerini E, Danesino C, et al. Management and treatment of glycogenosis type II. Neurology. Dec 2 2008;71(23 Suppl 2):S12-36. [Medline].

  4. Richard E, Douillard-Guilloux G, Caillaud C. New insights into therapeutic options for Pompe disease. IUBMB Life. Nov 2011;63(11):979-86. [Medline].

  5. Byrne BJ, Falk DJ, Pacak CA, Nayak S, Herzog RW, Elder ME, et al. Pompe disease gene therapy. Hum Mol Genet. Apr 15 2011;20:R61-8. [Medline]. [Full Text].

  6. Hagemans ML, Winkel LP, Van Doorn PA, et al. Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain. Mar 2005;128(Pt 3):671-7. [Medline]. [Full Text].

  7. Hagemans ML, Winkel LP, Hop WC, et al. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology. Jun 28 2005;64(12):2139-41. [Medline].

  8. Hagemans ML, Hop WJ, Van Doorn PA, et al. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology. Feb 28 2006;66(4):581-3. [Medline].

  9. Muller-Felber W, Horvath R, Gempel K, et al. Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients. Neuromuscul Disord. Oct 2007;17(9-10):698-706. [Medline].

  10. Van der Beek NA, Hagemans ML, Reuser AJ, 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].

  11. Papadimas GK, Spengos K, Papadopoulos C, Manta P. Late Onset Glycogen Storage Disease Type II: Pitfalls in the Diagnosis. Eur Neurol. Dec 15 2011;67(2):65-68. [Medline].

  12. Bembi B, Cerini E, Danesino C, et al. Diagnosis of glycogenosis type II. Neurology. Dec 2 2008;71(23 Suppl 2):S4-11. [Medline].

  13. Parenti G, Andria G. Pompe disease: from new views on pathophysiology to innovative therapeutic strategies. Curr Pharm Biotechnol. Jun 2011;12(6):902-15. [Medline].

  14. Van den Hout H, Reuser AJ, Vulto AG, et al. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet. Jul 29 2000;356(9227):397-8. [Medline].

  15. Rossi M, Parenti G, Della Casa R, et al. Long-term enzyme replacement therapy for Pompe disease with recombinant human alpha-glucosidase derived from Chinese hamster ovary cells. J Child Neurol. May 2007;22(5):565-73. [Medline].

  16. 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):210-219. [Medline].

  17. Schoser B, Hill V, Raben N. Therapeutic approaches in glycogen storage disease type II/Pompe Disease. Neurotherapeutics. Oct 2008;5(4):569-78. [Medline].

  18. Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. Feb 2000;18(1):151-65. [Medline].

  19. Behrman RE. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders; 2000:. 411-13.

  20. Bijvoet AG, Van Hirtum H, Kroos MA, et al. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet. Nov 1999;8(12):2145-53. [Medline].

  21. Bodamer OA, Halliday D, Leonard JV. The effects of l-alanine supplementation in late-onset glycogen storage disease type II. Neurology. Sep 12 2000;55(5):710-2. [Medline].

  22. Bradley WG. Neurology in Clinical Practice: The Neurological Disorders. 2nd ed. Boston, Mass: Butterworth-Heinemann; 1995:. 1537-38.

  23. Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine. 4th ed. Philadelphia, Pa: WB Saunders; 1992:. 995-6.

  24. Caliskan M, Yilmaz Y, Serdaroglu P, et al. Late infantile acid maltase deficiency: a case report. Turk J Pediatr. Jan-Mar 1999;41(1):121-5. [Medline].

  25. Chen YT, Amalfitano A. Towards a molecular therapy for glycogen storage disease type II (Pompe disease). Mol Med Today. Jun 2000;6(6):245-51. [Medline].

  26. Damjanov I, Linder J. Anderson's Pathology. 10th ed. St. Louis, Mo: Mosby; 1996:. 2699-2700.

  27. Goetz CG, Pappert EJ. Textbook of Clinical Neurology. Philadelphia, Pa: WB Saunders; 1999:. 571-3.

  28. McKusick VA. Mendelian Inheritance in Man. 10th ed. Baltimore, Md: Johns Hopkins University Press; 1992.

  29. McMillan JA. Oski's Pediatrics: Principles and Practice. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:. 1961, 1977-8.

  30. Mellies U, Ragette R, Schwake C, et al. Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology. Oct 9 2001;57(7):1290-5. [Medline].

  31. Melvin JJ. Pompe's disease. Arch Neurol. Jan 2000;57(1):134-5. [Medline].

  32. Poenaru L. Approach to gene therapy of glycogenosis type II (Pompe disease). Mol Genet Metab. Jul 2000;70(3):163-9. [Medline].

  33. Rowland LP. Merritt's Textbook of Neurology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1995:. 506.

  34. Scriver CR. The Metabolic Basis of Inherited Disease. 6th ed. New York, NY: McGraw-Hill; 1989:. 437-440.

  35. Selak MA, de Chadarevian JP, Melvin JJ, et al. Mitochondrial activity in Pompe's disease. Pediatr Neurol. Jul 2000;23(1):54-7. [Medline].

  36. Slonim AE, Bulone L, Ritz S, et al. Identification of two subtypes of infantile acid maltase deficiency. J Pediatr. Aug 2000;137(2):283-5. [Medline].

  37. Stryer L. Biochemistry. 3rd ed. New York, NY: WH Freeman & Co; 1988.

  38. Umapathysivam K, Whittle AM, Ranieri E, et al. Determination of acid alpha-glucosidase protein: evaluation as a screening marker for Pompe disease and other lysosomal storage disorders. Clin Chem. Sep 2000;46(9):1318-25. [Medline].

  39. van der Ploeg AT. Monitoring of pulmonary function in Pompe disease: a muscle disease with new therapeutic perspectives. Eur Respir J. Dec 2005;26(6):984-5.

  40. Vorgerd M, Burwinkel B, Reichmann H, et al. Adult-onset glycogen storage disease type II: phenotypic and allelic heterogeneity in German patients. Neurogenetics. Mar 1998;1(3):205-11. [Medline].

  41. Winkel LP, Kamphoven JH, van den Hout HJ, et al. Morphological changes in muscle tissue of patients with infantile Pompe's disease receiving enzyme replacement therapy. Muscle Nerve. Jun 2003;27(6):743-51. [Medline].

  42. Winkel LP, Van den Hout JM, Kamphoven JH, et al. Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up. Ann Neurol. Apr 2004;55(4):495-502.

 
Previous
Next
 
Glycogen molecule; by cleaving glycogen's 1,4 and 1,6 alpha-glycosidic linkages, the enzyme acid maltase gives rise to free glucose molecules.
Metabolic pathways of carbohydrates.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.