Acid α-Glucosidase (Pompe Disease)
Related Gene(s): GAA
Pompe disease is a glycogen storage disease affecting approximately 1 in 40,000 people in the general population of the United States. The disease is inherited in an autosomal recessive pattern and is caused by a deficiency of lysosomal acid α-glucosidase (GAA). GAA hydrolyzes the terminal a-linked glucose residues in short polymers of glucose when breakdown glycogen in tissues. Deficiency of GAA enzyme leads to a build-up of glycogen in lysosomes of cells causing damage to organs and tissues throughout the body especially in the muscle tissues. There are three classifications of Pompe disease: Classic infantile-onset Pompe disease, non-classic infantile-onset Pompe disease, and late-onset Pompe disease. All classifications range in age of onset, organ involvement, severity of symptoms, and speed of progression of disease. Symptoms of classic infantile-onset Pompe disease include poor feeding, failure to thrive, cardiomegaly and hypertrophic cardiomyopathy, generalized muscle weakness, respiratory distress, and hypotonia. Symptoms of late-onset Pompe disease include muscle weakness, respiratory issues, swallowing difficulties, and exercise intolerance. Severity varies with age of onset.
Diagnosis of Pompe disease can be established by demonstration of deficiency of GAA enzyme and identification of biallelic pathogenic GAA mutations. Complete or near absent GAA activity (less than 1%) is associated with classic infantile Pompe disease. Partial GAA deficiency (~2-10%) is associated with non-classic infantile and late-onset forms. Pseudodeficiency alleles can also result in reduced GAA activity. Assays of acid α-glucosidase enzyme activity in cultured skin fibroblasts or muscle used to be the gold standard for diagnosing Pompe disease. Now GAA activity can be reliably measured in leukocyte specimen using a liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. However, this assay is not reliable for detection of gene carriers. Carrier testing can be accomplished through molecular analysis of the GAA gene.
- Blood: 5-10 mL in ACD tube (yellow top) is preferred. Minimum of 3 mL is required. Sodium (or lithium) heparin tubes (green top) or EDTA tubes (lavender top) are also accepted
- 1-2 leukocyte pellets
- Ship whole blood at room temperature (sample must be received within 72 hours of collection)
- Ship leukocyte pellet(s) frozen on dry ice
- 7 days
- GAA molecular testing can be ordered for diagnostic purposes via the Expanded Carrier Screen panel