Acid Alpha-Glucosidase, Blood Spot
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase (GAA). This leads to an accumulation of glycogen in the lysosome causing swelling, cell damage, and progressive organ dysfunction. Pompe disease is caused by mutations in the GAA gene, and it is characterized by muscle hypotonia, weakness, cardiomegaly, hypertrophic cardiomyopathy, and eventual death due to either cardiorespiratory or respiratory failure. The clinical phenotype, in general, appears to be dependent on residual enzyme activity, with complete loss of activity causing onset in infancy. Untreated, this leads to death, typically within the first year of life. Juvenile and adult-onset forms are characterized by later onset and longer survival. Primary symptoms of later-onset Pompe disease include muscle weakness and respiratory insufficiency. Rarely, clinically significant cardiomyopathy can be seen. The estimated incidence is 1 in 40,000 live births.
Enzyme replacement therapy (ERT) improves outcome in many patients with either classic infantile onset or later onset forms of Pompe disease. Early initiation of treatment improves the prognosis and makes early diagnosis of Pompe disease desirable. Because of this, newborn screening for Pompe disease has recently been implemented in some states. The early identification and treatment of infants with Pompe disease has been shown to be helpful in reducing the morbidity and mortality associated with this disease.
Since Pompe disease is considered a rare condition that progresses rapidly in infancy, the disease, in particular the juvenile and adult-onset forms, is often considered late if at all, during the evaluation of patients presenting with proximal muscle weakness and respiratory insufficiency. Testing traditionally required a skin or muscle biopsy to establish cultures for enzyme testing. More recently, molecular genetic testing of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) became clinically available. Determination of the enzyme activity in dried blood spot specimens can be performed in a timely fashion and provide better guidance in the decision to submit samples for further confirmatory testing by molecular genetic analysis (GAAZ / Pompe Disease, Full Gene Analysis).
Evaluation of patients of any age with a clinical presentation suggestive of Pompe disease (muscle hypotonia, weakness, or cardiomyopathy)
Normal results (>0.5 nmol/hour/mL) in properly submitted specimens are not consistent with classic Pompe disease. Affected individuals typically have levels of 0.5 nmol/hour/mL or less; however, some later onset cases may show higher enzyme activity.
Results of 0.5 nmol/hour/mL or less can be followed up by molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) to determine carrier, pseudodeficiency, or disease status.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Specimens exposed to heat above 25 degrees C for more than 48 hours will yield higher activity levels than properly submitted specimens. This may cause false-normal (false-negative) results in affected patients.
Pseudodeficiency results in low measured GAA, but is not consistent with Pompe disease; GAAZ / Pompe Disease, Full Gene Analysis should be performed to resolve the clinical question.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal >0.5 nmol/mL/hour
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Chien YH, Hwu WL, Lee NC: Pompe Disease: early diagnosis and early treatment make a difference. Pediatr Neonatol 2013;54:219-227
2. Gungor D, Kruijshaar ME, Plug I, et al: Quality of life and participation in daily life of adults with Pompe Disease receiving enzyme replacement therapy: 10 years of international follow-up. J Inher Metab Dis 2015 Nov;38:495-503
3. Katzin LW, Amato AA: Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J Clin Neuromuscul Dis 2008 Jun;9(4):421-431
4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. McGraw-Hill, Medical Publishing Division, 2009, pp 750-751
5. Matern D, Gavrilov D, Oglesbee D, et al: Newborn screening for lysosomal storage disorders. Semin Perinatol 2015 Apr;39(3):206-216