glycogen storage disease II

Glycogen storage disease II, also known as Pompe disease or acid maltase deficiency, is a metabolic myopathy characterized by the buildup of glycogen within lysosomes. It is caused by pathogenic variants in the GAA gene that lead to deficient acid maltase enzyme activity. This condition classically presents in a spectrum that includes early onset forms, which are more severe and often fatal, as well as later onset forms that may have a slower progression. Precise prevalence estimates are not well established, and the condition is included in newborn screening programs as part of the RUSP CORE panel.

Individuals with glycogen storage disease II typically experience progressive muscle weakness, which often starts as proximal and lower limb muscle weakness. Early clinical features can include feeding difficulties in infancy, failure to thrive, and motor delay, while later manifestations may involve respiratory insufficiency, exercise intolerance, and characteristic signs such as Gowers sign. Cardiac involvement is seen in a subset of patients, as evidenced by findings like left ventricular hypertrophy and cardiomegaly, and additional features such as tongue fasciculations and hypomimic facial expressions have been noted. Not all individuals experience all features, and severity varies considerably.

Glycogen storage disease II results from pathogenic variants in the GAA gene, which encodes the acid maltase enzyme that is essential for breaking down glycogen in the lysosomes. The enzyme deficiency leads to the accumulation of glycogen in muscle and other tissues, ultimately causing the metabolic myopathy observed in affected individuals. The condition is inherited in an autosomal recessive manner, meaning that two copies of the altered gene, one inherited from each parent, are typically required for the disease to manifest. Genetic counseling is recommended for affected families to understand recurrence risks and implications for family planning.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for glycogen storage disease II. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the various aspects of the condition. Long-term management includes regular surveillance to detect complications early; for example, periodic assessment of respiratory and cardiac function is important given the potential involvement of these systems. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to help families understand the condition and plan for the future.

The clinical course of glycogen storage disease II is highly variable, with outcomes that depend on factors such as the age of onset, severity of symptoms, and access to specialized care. Although early onset forms tend to be more severe, many individuals benefit from current standards of care and ongoing surveillance, which has improved outcomes significantly over recent decades. With current management strategies, many individuals maintain a better quality of life, although the condition remains lifelong with potential for progression in motor and respiratory functions. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors for ongoing guidance.

Glycogen storage disease II is an active area of research with numerous ongoing clinical trials exploring new treatment approaches. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team to learn about potential eligibility for investigational therapies.