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 alterations in the GAA gene. The estimated incidence is 1 in 40,000 live births. In Pompe disease, glycogen is taken up by lysosomes during physiologic cell turnover and accumulates, causing lysosomal swelling and cell damage, which results in organ dysfunction. Symptoms include progressive muscle weakness, cardiomyopathy, and, eventually, death if untreated.

Clinically, Pompe disease is categorized into infantile and late-onset forms based on age of onset, organ involvement, and rate of progression. The infantile form (or classic Pompe disease) is the most severe variant and is characterized by early onset and rapid progression of cardiac, liver, and muscle problems resulting in death within the first year of life. The infantile variant of Pompe disease has a similar age of onset but a milder clinical presentation. Late-onset Pompe disease can present with muscle weakness, cardiomyopathy, and/or respiratory dysfunction in childhood or later, including advanced adulthood. The rate of progression and severity of symptoms is variable, particularly in the late-onset forms.

Treatment with enzyme replacement therapy (ERT) is available, making early diagnosis of Pompe disease desirable because early initiation of treatment improves the prognosis. Treatment with ERT can prolong survival in patients with infantile onset Pompe disease; however, the effectiveness of treatment is impacted by the presence or absence of cross-reactive immunologic material (CRIM) to the GAA enzyme. Patients who are CRIM-negative are more likely to develop antibodies against recombinant human GAA than patients who are CRIM-positive, thereby decreasing the effectiveness of treatment. Strategies to decrease the immune response to ERT, such as immunosuppression, rely on determination of CRIM status.

Molecular analysis of the GAA gene can determine CRIM status in over 90% of patients with Pompe disease (GAAZ / Pompe Disease, Full Gene Analysis, Varies). However, for those who have GAA variants not classified as either CRIM-negative or -positive, CRIM testing in fibroblasts or leukocytes can determine final CRIM status. Therefore, CRIM testing is useful for either confirmation of CRIM status determined by molecular testing or determination of CRIM status if the genotype is not informative.