Classic Infantile-Onset Pompe Disease

Pompe disease is a rare, inherited disorder caused by insufficient amounts or activity of an enzyme called acid alpha-glucosidase. People with Pompe disease have a mutation in the gene that provides instructions for this enzyme, which is necessary to break down glycogen, a complex sugar molecule, into glucose the body uses for energy. If glycogen is not broken down, it accumulates inside cells, especially muscle cells. This buildup damages cells, causing muscle weakness and wasting.

There are several types of Pompe disease classified by the time of onset and type of symptoms. In classic infantile-onset Pompe disease, symptoms such as cardiomyopathy or disease of the heart muscle appear before a baby reaches 12 months of age. In non-classic infantile-onset Pompe disease, symptoms still arise in infancy, but typically later in the first year. In this type, the heart may be enlarged, but there is less cardiomyopathy, and the condition causes more significant breathing problems. In late-onset Pompe disease, symptoms arise any time between late childhood and adulthood.


Symptoms of classic infantile-onset Pompe disease commonly begin around 4 months of age. They include poor feeding due to muscle weakness in the face and tongue, leading to slow growth (failure to thrive). Other symptoms include muscle weakness and delayed motor development, difficulty breathing and respiratory infections, and heart problems. Hearing loss is also common in babies with classic infantile-onset Pompe disease.


In some cases, symptoms of classic infantile-onset Pompe disease can be recognized before a baby is born, but the disease is often diagnosed in the first few months of life. In some states and countries, classic infantile-onset Pompe disease is part of newborn screening where a blood sample is used to look for the activity of the acid alpha-glucosidase enzyme.

A urine test to measure levels of tetrasaccharide, a type of sugar molecule, which is elevated in patients with classic infantile-onset Pompe disease may be used to follow up an abnormal newborn screening result. In addition, a blood test to measure serum creatine kinase may also be used. Creatine kinase is released into the blood by damaged muscle cells. But the results of these tests are less specific because these substances may also be elevated in other disorders.

A skin biopsy, where a small number of skin cells are taken to be grown in the laboratory, may also be done if classic infantile-onset Pompe disease is suspected. These skin cells are then tested for acid alpha-glucosidase enzyme activity. This test is more sensitive than the blood test, and can be used to distinguish between the different types of Pompe disease.

Genetic testing from a blood sample is considered the best diagnostic tool to confirm a diagnosis of classic infantile-onset Pompe disease. There are several types of tests including a single-gene test, a targeted analysis for specific gene variants, or a multigene panel. A deletion/duplication analysis is recommended to check for mutations that may not be detected by a standard genetic sequence analysis.

Following diagnosis, a number of tests are performed to evaluate the severity of the disease and the baby’s needs. These include assessments of heart and lung function, hearing, nutrition and feeding, and motor skills.


It is recommended that babies with classic infantile-onset Pompe disease begin treatment with enzyme replacement therapy (ERT) as soon as possible. In ERT, the patient is regularly treated with a synthetic copy of the acid alpha-glucosidase enzyme. Lumizyme (alglucosidase alfa) is a medication that mimics the action of the acid alpha-glucosidase enzyme and helps reduce the accumulation of glycogen, preventing muscle damage that leads to the symptoms of classic infantile-onset Pompe disease.

A study showed that babies treated with ERT before 6 months of age and before they required a ventilator had improved survival, reduced need for ventilators, improved acquisition of motor skills, and better heart health, compared with babies who did not receive ERT.

Babies who receive ERT may develop an immune response to the treatment. This can reduce the effectiveness of ERT, and many doctors recommend babies receive medications to reduce this immune response early on in ERT.

Most patients also require supportive therapy to address the symptoms of classic infantile-onset Pompe disease such as respiratory problems, physical disability, and difficulty swallowing. Some may require a mechanical ventilator during respiratory infections or at night. It is important that babies and household members keep their vaccinations up to date to reduce the risk of these infections. Infants with classic infantile-onset Pompe disease may need a feeding tube to ensure adequate nutrition.


Improvements in treatments, early diagnosis, and early treatment with ERT are improving outcomes significantly for babies with classic infantile-onset Pompe disease. However, since these developments are still relatively new, there is limited information on their long-term outcomes, especially in the case of ERT early in life.

It does appear that babies treated with ERT have better health and live longer than babies who are not treated, with those untreated typically dying before 2 years old due to heart and/or respiratory failure.

Researchers are working on new treatments including medications that will improve the effectiveness of ERT and gene therapy approaches that address the underlying genetic cause of Pompe disease.


Pompe Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.