What is Pompe disease (Glycogen storage disease type II)?

From the Guidelines

Pompe disease is a rare genetic disorder characterized by the deficiency of an enzyme called acid alpha-glucosidase (GAA), which is needed to break down glycogen in the body, and it is diagnosed and managed based on the latest guidelines and evidence, including biomarker testing and enzyme replacement therapy (ERT) 1. The disease exists in different forms, including infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), with varying ages of onset and severity of symptoms. According to the latest evidence, IOPD is apparent shortly after birth and presents with hypotonia, muscle weakness, failure to thrive, and hypertrophic cardiomyopathy, while LOPD presents anytime between late infancy and adulthood with a myopathy that progresses to respiratory insufficiency if left untreated 1.

Key Characteristics of Pompe Disease

• Autosomal recessive inheritance pattern
• Deficiency of acid alpha-glucosidase (GAA) enzyme
• Accumulation of glycogen in various tissues, particularly in the heart, skeletal muscles, and liver
• Progressive muscle weakness and organ dysfunction
• Different forms, including infantile, juvenile, and adult-onset

Diagnosis and Management

• Early diagnosis through newborn screening or genetic testing is crucial for prompt treatment initiation
• Biomarker testing, such as urinary Glc 4 excretion, can assist in distinguishing patients with IOPD from LOPD 1
• Enzyme replacement therapy (ERT) with medications like alglucosidase alfa (Myozyme or Lumizyme) is the primary treatment, administered intravenously every two weeks to replace the missing enzyme
• Supportive care, including respiratory support, physical therapy, and dietary management, is also essential

Importance of Early Diagnosis and Treatment

• Prompt treatment initiation can significantly improve outcomes and quality of life for patients
• Early diagnosis and treatment can reduce the risk of complications, such as heart failure and respiratory failure
• Biomarker testing and ERT can help monitor response to treatment and adjust management plans as needed 1

From the FDA Drug Label

Pompe disease (acid maltase deficiency, glycogen storage disease type II, GSD II, glycogenosis type II) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA. Pompe disease is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA 2.

• It is also known as acid maltase deficiency, glycogen storage disease type II, GSD II, or glycogenosis type II.
• The disease is caused by a deficiency of the enzyme GAA, which is necessary for the breakdown of glycogen in the body.
• Alglucosidase alfa provides an exogenous source of GAA, which helps to break down glycogen and alleviate the symptoms of the disease 2.

From the Research

Definition and Cause of Pompe Disease

• Pompe disease is a rare autosomal recessive disorder caused by mutations in the GAA gene, which encodes for acid alpha-1,4-glucosidase (GAA) 3.
• The GAA gene is localized on chromosome 17, and more than 560 mutations have been reported throughout the gene 3.
• The deficiency of GAA leads to lysosomal storage of glycogen in several tissues, particularly in muscle, resulting in a chronic and progressive pathology 3.

Clinical Manifestations

• Pompe disease is characterized by limb-girdle muscle weakness and respiratory failure 3.
• The disease is classified into infantile and childhood/adult forms, with patients exhibiting a multisystemic manifestation that depends on the age of onset 3.
• Cardiomyopathy and skeletal muscle myopathy are observed in patients with complete enzyme deficiency, while skeletal muscle myopathy leading to respiratory insufficiency is the predominant manifestation of partial enzyme deficiency 4.

Treatment and Therapies

• Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) is a lifesaving treatment for the most severe form of the disease and provides clinically meaningful benefits to patients with milder phenotypes 5, 6.
• Newer ERTs, such as avalglucosidase alfa and cipaglucosidase alfa, have been developed to improve patient outcomes beyond alglucosidase alfa 5, 6.
• Other potential therapeutic strategies include substrate reduction therapy, which reduces intracellular glycogen concentrations, and gene therapy, which may restore endogenous production of deficient acid alpha-glucosidase 5, 7.

Pathogenesis and Diagnosis

• The accumulation of glycogen in lysosomes due to GAA deficiency leads to progressive muscle weakness and metabolic dysregulation 3, 7.
• Early diagnosis is essential to prevent or reduce the irreversible organ damage associated with Pompe disease progression 3.
• Biomarkers, such as miRNAs, may play a role in the diagnosis and monitoring of Pompe disease 3.