Pompe

Classic form of the disease presents with hypertrophic cardiomyopathy and heart failure. 

Both infantile-onset and late-onset forms can present with muscle weakness and respiratory failure. Other shared clinical features may include heart abnormalities, hepatosplenomegaly and macroglossia.

However, the severity and onset of these symptoms can differ between the two forms of the disease, with the infantile-onset form being more severe and life-threatening than the late-onset form.

Infantile onset - Classic subtype: This type presents within a few months after birth and is characterized by the following:

• Hypotonia since birth.
• Hyporeflexia/areflexia. 
• Contractures and joint deformities, such as lordosis and scoliosis.
• Pneumonia and upper respiratory tract infection.
• Respiratory insufficiency.
• Hypertrophic cardiomyopathy.
• Congestive heart failure.
• Conduction disorders.

Adult onset - This type is characterized by the following:

• Progressive limb-girdle weakness followed by the diaphragm and accessory respiratory muscles.
• Hyporeflexia.
• Gait disturbances.
• Myalgia and cramps.
• Amyotrophy.
• Dyspnea on exertion.
• Orthopnea.
• Sleep apnea.
• Frequent respiratory tract infections.

Blood biochemistry analysis can provide important information for diagnosing Pompe disease, with elevated levels of creatine kinase (CK), transaminases, and lactate dehydrogenase (LDH) being sensitive but nonspecific indicators. 

Measurement of α-glucosidase activity in dried blood spots (DBS) is essential for diagnosis, along with confirmatory tests such as enzyme studies and genetic testing searching for GAA mutation. 

Imaging tests such as muscle MRI and chest radiography can provide valuable information, with echocardiography being particularly useful for detecting cardiac abnormalities.¹

Currently, there is no cure for Pompe. Enzyme replacement therapy (ERT) has been a major therapeutic advancement and is the treatment of choice. ERT has been shown to improve patients’ lives, however, its benefits may be attenuated by antibody formation, therefore combining ERT with enzyme stabilizers is being investigating to enhance treatment efficacy.

The most serious complication is progressive muscle weakness, which can result in respiratory failure and ultimately, death. Other potential complications include developmental delays, feeding difficulties, aspiration pneumonia, and hearing loss. Without treatment, the infantile form of Pompe disease can be life-threatening, and many infants do not survive beyond their first year.