Classic infantile-onset Pompe Disease
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Classic infantile-onset, and nonclassic infantile-onset are two of the three types of Pompe disease, with the third type known as late-onset. Different types are determined by age of onset, the severity of the symptoms, and organ involvement.
Classic infantile-onset Pompe disease is the most severe form of the disease. Symptoms such as cardiomyopathy (disease of the heart muscle) usually appear before an infant reaches 12 months of age.
Nonclassic infantile Pompe disease is less severe, with slower progression of symptoms. Some people with this form of the disease can have an enlarged heart, but cardiomyopathy is usually not present during the first year of life. Children can typically be diagnosed with this type later in the first year of life.
Causes
Pompe disease is a rare, inherited disorder, caused by insufficient amounts or activity of an enzyme called acid alpha-glucosidase.
All people with Pompe disease have a mutation in the GAA gene that provides instructions for the production of this enzyme, which is necessary to break down a complex sugar molecule called glycogen into glucose, which 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 and, eventually, death from heart and respiratory failure.
Symptoms
Symptoms are different for classic infantile-onset Pompe disease and the nonclassic type, although there are some similarities.
Symptoms of classic infantile-onset Pompe disease
Symptoms of classic infantile-onset Pompe disease commonly begin around within the first few months of life.
They include:
- poor feeding due to muscle weakness in the face and tongue
- slow growth (failure to thrive)
- muscle weakness
- delayed motor development
- difficulty breathing and respiratory infections
- heart problems
- hearing loss.
Without treatment, babies with classic infantile-onset Pompe disease may die before age 2 from heart problems and respiratory failure.
Symptoms of nonclassic infantile-onset Pompe disease
Nonclassic infantile-onset symptoms may start before or after 12 months of age, and are usually less severe. Children can show:
- progressive muscle weakness
- delayed development of motor skills, such as rolling over and sitting up.
The heart also is less likely to be affected in nonclassic infantile-onset Pompe disease. Some patients may experience cardiomegaly (an enlarged heart), which can lead to heart failure if untreated, but progression is generally slower. Progressive muscle weakness can also lead to severe breathing problems and lung failure if untreated.
Diagnosis
A definite diagnosis of Pompe disease requires genetic testing and enzyme activity tests.
In some U.S. states and internationally, Pompe disease can form part of newborn screening where a blood sample is used to look for the activity of the acid alpha-glucosidase enzyme.
A skin biopsy, where a small number of skin cells are taken to be grown in the laboratory, may be done if classic infantile-onset Pompe disease is suspected. These skin cells are tested for acid alpha-glucosidase enzyme activity. According to the National Organization for Rare Disorders (NORD), 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 including GAA and other genes of interest for a differential diagnosis.
A urine test to measure levels of tetrasaccharide, a type of sugar molecule, which is elevated in patients with 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 result of this test is not Pompe disease-specific as high levels of creatine kinase may also be seen.
A chest X-ray may show the infant has cardiomegaly, while electrocardiography may show hypertrophy of one or both ventricles in the heart, which is when these heart chambers responsible for pumping blood become thicker and may no longer be able to function properly.
Other diseases which may resemble infantile-onset Pompe disease include a number of types of muscular dystrophy, such as limb-girdle muscular dystrophy, Duchenne muscular dystrophy, and Becker muscular dystrophy, along with myasthenia gravis, Danon disease, and chronic fatigue syndrome.
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.
Prognosis and treatment
Improvements in treatments, early diagnosis, and early treatment with enzyme replacement therapy (ERT), are improving outcomes for babies with infantile-onset Pompe disease. However, as these developments are still relatively new, there is limited information on long-term outcomes, especially in the case of ERT early in life.
It does appear children with classic infantile-onset disease treated with ERT have better health and live longer than babies who are not treated, with those untreated typically dying before 2 years of age due to heart and/or respiratory failure.
It is recommended that babies with infantile-onset Pompe disease begin treatment with ERT as early as possible.
In the U.S., Lumizyme (alglucosidase alfa; marketed under the brand name Myozyme outside the U.S.) is an approved ERT that is used to reduce the accumulation of glycogen, preventing muscle damage that leads to the symptoms of both types of infantile-onset Pompe disease.
A study showed that babies treated with ERT younger than 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.
Most babies also require supportive therapy to help address the symptoms of 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. Babies with infantile-onset Pompe disease may need a feeding tube to ensure adequate nutrition.
Researchers are working on new treatments including medications to improve the effectiveness of ERT and gene therapy approaches that address the underlying genetic cause of Pompe disease.
Life expectancy
Unfortunately, life expectancy for both types of infantile-onset Pompe disease is short.
Without treatment, children with classic infantile-onset Pompe disease usually die within the first two years.
Nonclassic infantile-onset Pompe disease often results in death in early childhood, although treatment may further slow the progression of symptoms.
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.
FAQs about infantile-onset Pompe disease
The two types of infantile-onset Pompe disease are classic infantile-onset and nonclassic infantile onset. They differ in the age of onset and the severity of symptoms.
At this point in time, there is no cure for infantile-onset Pompe disease. Treatment consists of enzymatic replacement therapy, along with treatment for cardiac and respiratory difficulties, and other health issues.
Infantile-onset Pompe disease is rare, with an estimated worldwide incidence of around 1 in 150,000 births. Of note, the incidence of infantile-onset disease seems to be affected by ethnicity, with an estimated incidence of 1 in 130,000 births in the Caucasian population, 1 in 50,000 in the Chinese population, and 1 in 31,000 among African ancestry populations.
Pompe disease is an inherited disorder. For a person to develop the disease, one needs to inherit two mutated copies of the GAA gene, one from each biological parent. Mutations in the GAA gene lead to absent or reduced levels of an enzyme that metabolizes the breakdown of a complex sugar called glycogen.
Unfortunately, life expectancy for children with infantile-onset Pompe disease is short. Without treatment, children with classic infantile-onset Pompe disease (the most severe form of the disease) usually die within the first two years of life. Severe muscle weakness can lead to respiratory failure and death in children with the nonclassic infantile-onset type by early childhood.
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