Also known as: acid maltase deficiency (AMD); glycogen storage disease type II; type II glycogenosis

Metabolic defect: acid alpha-glucosidase (GAA) deficiency

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Decreased glycogen degradation in lysosomes leads to accumulation in virtually every tissue. Primary cellular pathways for the breakdown of glycogen remain intact (via cellular alpha-D-glucose l-phosphate), but these are not available in lysosomes.

Macroglossia		Cardiomegaly		Floppy baby/muscle weakness

Pompe disease is an autosomal recessive genetic disorder caused by a deficiency or dysfunction of the lysosomal hydrolase acid alpha-glucosidase (GAA). This enzymatic defect results in lysosomal glycogen accumulation in multiple tissues, with cardiac and skeletal muscle tissues most seriously affected. Pompe disease manifests as a spectrum of severity, ranging from a rapidly fatal infantile-onset form to a more slowly progressive late-onset myopathy. Given time, all clinical phenotypes will progress from mild to severe symptomatology.

Symptom onset at or shortly after birth including progressive muscle weakness, severe hypotonia (“floppy baby” appearance), cardiomegaly, cardiomyopathy, delayed developmental milestones, respiratory insufficiency, frequent respiratory infections and feeding difficulties.

Death from cardiorespiratory failure typically occurs by 12 months of age.

Symptom onset from early childhood through adulthood including

progressive myopathy (primarily in the muscles of the trunk, lower limbs, and diaphragm), respiratory insufficiency, gait abnormalities, sleep apnea and fatigue, and delayed motor milestones (in children)

Death usually results from respiratory failure

Infantile-onset:

Difficulty swallowing, sucking, and/or feeding

Failure to thrive

Hepatomegaly (moderate)

Late-onset:

Hepatomomegaly

Infantile-onset:

Progressive muscle weakness

Profound hypotonia (“floppy” baby appearance)

Failure to achieve motor milestones

Laxity of facial muscles

Macroglossia (and in some cases, protrusion of the tongue)

Areflexia

Late-onset:

Progressive proximal muscle weakness

Delayed motor milestones (children)

Gait abnormalities

Gower sign

Exercise intolerance

Scoliosis, lordosis, and / or kyphosis

Lower back pain

Hypotonia

Decrease deep tendon reflexes

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Infantile-onset:

Respiratory insufficiency

Progressive respiratory involvement

Frequent respiratory infections

Late-onset:

Respiratory insufficiency

Frequent respiratory infections

Sleep apnea

Somnolence

Exertional dyspnea

Orthopnea

Infantile-onset:

Progressive cardiomyopathy

Cardiomegaly (massive) and/or cardiac failure

Heart failure

Late-onset:

Infrequent cardiomegaly (juveniles)

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1. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid Alpha-glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill, 2001. 3389-3420.

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

3

. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of Lysosomal Storage Disorders. JAMA. 1999; 281: 249-254.

4. Personal communication with Dr. Priya Kishnani, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.

5. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid-Alpha Glucosidase (Acid Maltase) Deficiency. In: Wonsiewicz M, Noujaim S, Boyle P, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill; 2001; 3389-3420.

6. King, Frank J. Acid Maltase Deficiency Myopathy. eMedicine Specialties. Available at: http://www.emedicine.com/pmr/topic2.htm . Accessed November 7, 2002.

7. Ibrahim, Jennifer. Glycogen Storage Disease Type II. eMedicine Specialties. Available at: http://www.emedicine.com/ped/topic1866.htm Accessed November 7, 2002.