Sections

Type II Glycogen Storage Disease (Pompe Disease)

Sections Type II Glycogen Storage Disease (Pompe Disease)
Overview
Presentation
DDx
Workup
Treatment
Medication
References

Presentation

History

In the infantile classic subtype form, the caregiver may report feeding difficulties and difficulty breathing.^[10]The child may also have an enlarged tongue and poor muscle tone.

In the infantile non-classic subtype form, delayed motor skills such as rolling over and sitting up may be reported.

In the adult form, the patient may report progressive limb-girdle weakness, with the pelvic muscle more affected than the scapulohumeral group.The patient may also report early tiredness and fatigue, along with sleep-disordered breathing.

Physical Examination

1. Infantile onset - Classic subtype: This type presents within a few months after birth and is characterized by the following:

Neuromuscular manifestations

Hypotonia since birth
Hyporeflexia/areflexia
Muscle weakness
Contractures and joint deformities, such as lordosis and scoliosis, can occur because of compensatory movement patterns due to extensive weakness and limited mobility

Respiratory system

Respiratory muscle weakness can cause repeated episodes of pneumonia and upper respiratory tract infection
Respiratory insufficiency leads to early morbidity and mortality

Cardiovascular system

Hypertrophic cardiomyopathy
Congestive heart failure
Conduction disorders

Gastrointestinal and nutritional manifestations

Macroglossia
Difficulty in sucking due to facial hypotonia, oral motor weakness, and macroglossia; this can affect growth and weight gain
Hepatomegaly
Splenomegaly

2. Infantile onset - Non-classic subtype: This type usually presents within the first year of life and is less severe compared with the classic subtype; it is characterized by the following:

Delayed motor skills, such as sitting up and rolling over
Progressive muscle weakness
Cardiomegaly - Less likely compared with the classic subtype
Respiratory insufficiency

3. Adult onset: This type is characterized by the following:

Musculoskeletal system

Progressive limb-girdle weakness followed by diaphragm and accessory respiratory muscles
Hyporeflexia
Gait disturbances
Myalgia and cramps
Amyotrophy
Fatigue and tiredness - Exercise intolerance

Respiratory system

Dsypnea on exertion
Orthopnea
Sleep-disordered breathing
Sleep apnea
Weak cough
Frequent respiratory tract infections

Additional features

Dysphagia
Difficulty in chewing
Weight loss
Subarachnoid hemorrhage - Especially in the basilar artery

Differential Diagnoses

Lukacs Z, Nieves Cobos P, Mengel E, et al. Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening. J Inherit Metab Dis. 2010 Feb. 33 (1):43-50. [QxMD MEDLINE Link].
Kishnani PS, Beckemeyer AA, Mendelsohn NJ. The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. Am J Med Genet C Semin Med Genet. 2012 Feb 15. 160(1):1-7. [QxMD MEDLINE Link].
Herzog A, Hartung R, Reuser AJ, Hermanns P, Runz H, Karabul N, et al. A cross-sectional single-centre study on Pompe disease in 42 German patients: Molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations. Orphanet J Rare Dis. 2012 Jun 7. 7(1):35. [QxMD MEDLINE Link].
Bijvoet AG, Van Hirtum H, Vermey M. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. J Pathol. 1999 Nov. 189(3):416-24. [QxMD MEDLINE Link].
Gort L, Coll MJ, Chabas A. Glycogen storage disease type II in Spanish patients: High frequency of c.1076-1G>C mutation. Mol Genet Metab. 2007 Sep-Oct. 92(1-2):183-7. [QxMD MEDLINE Link].
Martiniuk F, Chen A, Mack A. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet. 1998 Aug 27. 79(1):69-72. [QxMD MEDLINE Link].
Chien YH, Lee NC, Thurberg BL, et al. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009 Dec. 124(6):e1116-25. [QxMD MEDLINE Link].
Burton BK. Newborn screening for Pompe disease: an update, 2011. Am J Med Genet C Semin Med Genet. 2012 Feb 15. 160(1):8-12. [QxMD MEDLINE Link].
Mah C, Cresawn KO, Fraites TJ Jr, Pacak CA, Lewis MA, Zolotukhin I. Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Gene Ther. 2005 Sep. 12(18):1405-9. [QxMD MEDLINE Link].
Jones HN, Muller CW, Lin M, et al. Oropharyngeal dysphagia in infants and children with infantile Pompe disease. Dysphagia. 2010 Dec. 25 (4):277-83. [QxMD MEDLINE Link].
Musumeci O, la Marca G, Spada M, et al. LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population. J Neurol Neurosurg Psychiatry. 2016 Jan. 87 (1):5-11. [QxMD MEDLINE Link].
Aminoff MJ. Electromyography in Clinical Practice. New York, NY: Churchill Livingstone; 1998.
Kansagra S, Austin S, DeArmey S, Kishnani PS, Kravitz RM. Polysomnographic findings in infantile Pompe disease. Am J Med Genet A. 2013 Dec. 161A (12):3196-200. [QxMD MEDLINE Link].
Feeney EJ, Austin S, Chien YH, et al. The value of muscle biopsies in Pompe disease: identifying lipofuscin inclusions in juvenile- and adult-onset patients. Acta Neuropathol Commun. 2014 Jan 2. 2:2. [QxMD MEDLINE Link].
Zingone A, Hiraiwa H, Pan CJ. Correction of glycogen storage disease type 1a in a mouse model by gene therapy. J Biol Chem. 2000 Jan 14. 275(2):828-32. [QxMD MEDLINE Link].
Taglia A, Picillo E, D'Ambrosio P, Cecio MR, Viggiano E, Politano L. Genetic counseling in Pompe disease. Acta Myol. 2011 Dec. 30(3):179-81. [QxMD MEDLINE Link]. [Full Text].
Phupong V, Shotelersuk V. Prenatal exclusion of Pompe disease by electron microscopy. Southeast Asian J Trop Med Public Health. 2006 Sep. 37(5):1021-4. [QxMD MEDLINE Link].
Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006 May. 8 (5):267-88. [QxMD MEDLINE Link].
Ambrosino N, Confalonieri M, Crescimanno G, Vianello A, Vitacca M. The role of respiratory management of Pompe disease. Respir Med. 2013 Aug. 107(8):1124-32. [QxMD MEDLINE Link].
Angelini C, Nascimbeni AC, Semplicini C. Therapeutic advances in the management of Pompe disease and other metabolic myopathies. Ther Adv Neurol Disord. 2013 Sep. 6(5):311-21. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Glycogen storage disease, type II. Metabolic pathways of carbohydrates.

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Author

Ricardo R Correa Marquez, MD, EsD, FACP, FACE, FAPCR, CMQ, ABDA, FACHT Associate Professor of Medicine, Program Director, Endocrinology, Diabetes and Metabolism Fellowship Program, Director for Diversity in Graduate Medical Education, University of Arizona College of Medicine-Phoenix; Assistant Professor of Medicine, Mayo College of Medicine, Mayo Clinic Arizona; Staff Endocrinologist, Phoenix Veterans Hospital (VAMC)

Ricardo R Correa Marquez, MD, EsD, FACP, FACE, FAPCR, CMQ, ABDA, FACHT is a member of the following medical societies: Academy of Physicians in Clinical Research, American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Healthcare Trustees, American College of Physicians, American Medical Association, American Thyroid Association, Association of Program Directors in Endocrinology, Endocrine Society, National Hispanic Medical Association, World Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Mythili Menon Pathiyil, MBBS

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for Physician Leadership, American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society, International Society for Clinical Densitometry, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Wayne E Anderson, DO, FAHS, FAAN Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO, FAHS, FAAN is a member of the following medical societies: American Academy of Neurology, American Headache Society, California Medical Association, California Neurology Society, International Headache Society, San Francisco Medical Society, San Francisco Neurological Society

Disclosure: Nothing to disclose.

Acknowledgements

Barry J Goldstein, MD, PhD Director, Division of Endocrinology, Diabetes and Metabolic Diseases, Professor, Department of Internal Medicine, Thomas Jefferson University

Barry J Goldstein, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and The Endocrine Society

Disclosure: Nothing to disclose.

Sections Type II Glycogen Storage Disease (Pompe Disease)
Overview
Presentation
DDx
Workup
Treatment
Medication
References

Type II Glycogen Storage Disease (Pompe Disease) Clinical Presentation

History

Physical Examination

References

Tables

Contributor Information and Disclosures

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