Pompe disease is a rare genetic disorder impacting the body’s ability to process glycogen, a complex sugar. It arises from a deficiency of the acid alpha-glucosidase (GAA) enzyme, which breaks down glycogen within cells. When GAA is missing or not functioning correctly, glycogen accumulates to harmful levels, particularly in muscle cells, impairing their function. Newborn screening detects such conditions early.
Why Newborn Screening Matters
Pompe disease is progressive, and early detection through newborn screening can significantly improve health outcomes. Different forms exist, including infantile-onset and late-onset, which vary in severity and onset age.
Infantile-onset Pompe disease is the most severe form, often appearing within the first few months of life. It is characterized by rapid progression of muscle weakness, poor muscle tone, an enlarged liver, and heart defects. Without timely intervention, this form can lead to heart failure and death within the first year or two of life.
The non-classic infantile-onset form typically appears by age one, presenting with delayed motor skills and progressive muscle weakness, though heart failure is less common than in the classic form. Late-onset Pompe disease can manifest later in childhood, adolescence, or adulthood, and is usually milder with less heart involvement. It primarily causes progressive muscle weakness, potentially leading to respiratory failure. Early diagnosis allows for prompt treatment before significant damage occurs, improving prognosis for affected infants.
The Screening Procedure
Newborn screening for Pompe disease involves a heel prick to collect a small blood sample shortly after birth. This typically occurs within 24 to 48 hours. A few drops of blood are placed onto a filter paper to create a dried blood spot, which is then sent to a laboratory for analysis.
The sample is tested for the activity of the acid alpha-glucosidase (GAA) enzyme, which is deficient in individuals with Pompe disease. Low GAA enzyme activity indicates a higher risk. This screening is part of a broader panel of tests conducted on newborns, aiming to identify serious but treatable conditions early.
What a Positive Screen Means
A positive newborn screen for Pompe disease does not confirm a diagnosis; it indicates further testing is necessary. If a baby has low GAA enzyme activity on the initial screen, additional confirmatory diagnostic tests are recommended. These follow-up tests may include measuring GAA enzyme activity in a different tissue sample, such as cultured skin fibroblasts or lymphocytes, for a more definitive assessment.
Genetic testing identifies specific mutations in the GAA gene, which causes Pompe disease. This analysis helps confirm the diagnosis and distinguish true Pompe disease from a “pseudodeficiency allele,” which can cause low enzyme levels on screening but does not lead to the disease. Genetic counseling is offered, helping families understand the inheritance pattern, genetic risks, and available options.
Managing Pompe Disease After Diagnosis
Once Pompe disease is diagnosed, the primary treatment is Enzyme Replacement Therapy (ERT). ERT provides a manufactured version of the missing GAA enzyme, administered intravenously. This enzyme helps break down accumulating glycogen in cells, slowing disease progression and improving muscle function. ERT is a lifelong treatment, usually given every two weeks, and has been shown to extend survival, particularly for infants with the severe infantile-onset form.
Supportive care complements ERT, tailored to individual needs. This may include respiratory support, such as mechanical ventilation, to manage breathing problems from muscle weakness. Nutritional management often involves a high-protein, controlled-carbohydrate diet to reduce glycogen buildup and support muscle health.
Physical and occupational therapy help maintain muscle strength, improve mobility, prevent contractures, and assist with daily living activities. Treatment is managed by a multidisciplinary medical team, including neurologists, cardiologists, pulmonologists, dietitians, and therapists, to address varied symptoms.