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 organ dysfunction. This leads to progressive muscle weakness, cardiomyopathy, and eventually, death. Individuals with Pompe disease, especially those with infantile, childhood, and juvenile onset, can have elevations of serum enzymes (eg, creatine kinase) secondary to cellular dysfunction.

The clinical phenotype of Pompe disease lies on a spectrum 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 individuals with all forms of Pompe disease, even before onset of symptoms. Unaffected individuals with GAA pseudodeficiency alleles and carriers may also be identified by newborn screening.

Determination of GAA enzyme activity in leukocytes can help distinguish between infantile and later onset Pompe disease, but it may also be deficient in individuals with pseudodeficiency alleles and in some carriers. Urine glucotetrasaccharides (HEX4 / Glucotetrasaccharides, Random, Urine) have been shown to be elevated in some individuals, particularly those with infantile onset, and may aid in the initial diagnosis and treatment monitoring.

Molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis, Varies) is necessary for differentiating alterations from disease-causing variants in affected individuals and for carrier detection in family members.