Clinical Information

Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA; acid maltase) due to variants in the GAA gene. The estimated incidence is 1 in 40,000 live births. In Pompe disease, glycogen that is taken up by lysosomes during physiologic cell turnover accumulates, causing lysosomal swelling, cell damage, and eventually, organ dysfunction. This leads to progressive muscle weakness, cardiomyopathy, and eventually, death. Patients with Pompe disease, especially those with infantile, childhood, and juvenile onset, can have elevated serum enzymes (such as creatine kinase) secondary to cellular dysfunction.

The clinical phenotype of Pompe disease lies on a spectrum, with differing clinical phenotypes dependent on age of onset and residual enzyme activity. Complete loss of enzyme activity causes onset in infancy leading to death, typically within the first year of life, when left untreated. Juvenile and adult-onset forms, as the names suggest, are characterized by later onset and longer survival. All disease variants are eventually associated with progressive muscle weakness and respiratory insufficiency. Cardiomyopathy is associated almost exclusively with the infantile form. Treatment with enzyme replacement therapy is available, making early diagnosis of Pompe disease desirable, as early initiation of treatment may improve prognosis. Newborn screening can identify patients with all forms of Pompe disease, even before onset of symptoms. Newborn screening may also identify unaffected patients with GAA pseudodeficiency alleles and carriers.

The ratio calculated using the creatine:creatinine ratio as the numerator and the activity of GAA as the denominator can differentiate true cases of infantile and late-onset Pompe disease from false-positive cases, such as carriers and pseudodeficiency of GAA enzyme. When applied to the newborn screening setting, this second-tier testing can provide results in a timely fashion and provide guidance in the decision to submit samples for additional confirmatory testing by molecular genetic analysis (GAAZ / Pompe Disease, Full Gene Analysis, Varies).