Types of Pompe Disease

Medically Reviewed by Renee A. Alli, MD on April 09, 2024
4 min read

Pompe disease is a single disorder, caused by inherited changes in a gene that affect how an enzyme in your body breaks down sugars for energy. A sugar called glycogen then builds up in your muscle cells. This causes muscle weakness that gets worse over time. 

But the disease has three distinct types. They have slightly different symptoms, show up at different ages, and vary in how serious they are. In some people, the affected enzyme doesn't work at all. In others, it still works to some extent.

Scientists classify the types of Pompe disease according to when symptoms first appear. They are:

  • Classic infantile-onset
  • Non-classic infantile-onset
  • Late-onset


The classic infantile-onset type usually shows up within the first 3 months after a baby's birth. It's the most serious form, and the main symptoms are weak muscles and poor muscle tone.

 “When you hold a newborn with classic infantile-onset disease, they flop like a rag doll,” says Gerard Vockley, MD, PhD, chief of genetic and genomic medicine at UPMC Children’s Hospital of Pittsburgh.

Other signs include:

  • Breathing problems, due to weak diaphragm muscles
  • An enlarged liver
  • Abnormally thick heart muscles
  • Failure to gain weight or grow as expected. This often happens because the baby has trouble feeding because of their weak muscles.
  • Hearing problems
  • An unusually large tongue
  • Resting their legs in a “frog" position

Babies with this form of Pompe disease need treatment with enzyme replacement therapy (ERT) right away. If left untreated, they usually die from heart failure within their first year. In this ongoing treatment, you get a man-made version of the faulty enzyme through an IV.

ERT can be very effective, says Christina Grant, MD, PhD, co-director of the Lysosomal Storage and Treatment Program at Children’s National Hospital in Washington, DC.  

“When babies with symptoms of Pompe disease are treated with enzyme replacement therapy, it helps preserve their organ function and prevents the condition from worsening,” she says. “Patients who were in the clinical trials for ERT as infants 20 years ago are alive today and doing well.”

In some states, infants are tested for Pompe disease as part of a routine newborn screening panel. Or a doctor may notice muscle problems.

Sometimes, the newborn screening picks up Pompe disease, but the child doesn't develop symptoms until years later, Vockley says. If your child tests positive but has no symptoms, doctors will monitor them with tests of their heart, lungs, and muscles. When and if problems arise, they'll start ERT.

“It seems that the prevalence of Pompe disease is much higher than we thought even a decade ago, since we’re simply finding more babies with it on the newborn screen,” says Grant. In some cases, she says, “these children may have genetic and enzyme changes, but they don’t have sick muscles.”

This form of disease tends to be less severe than classic infantile-onset, but usually emerges within the first year of life, says Grant. Signs include:

  • Muscle weakness that gets worse over time
  • Delayed motor skills, such as rolling over or sitting
  • An abnormally large heart
  • Breathing problems

This type of Pompe disease may go undiagnosed for longer, as symptoms are more subtle than classical infantile Pompe disease, Vockley says.

“Sometimes, an infant will be diagnosed with a gross motor delay, or a developmental delay, and a pediatrician won’t necessarily look deeper to see if there is a genetic disease behind it,” he explains. “But early diagnosis is crucial, because we know the earlier we give children ERT, the better their prognosis.”

Without ERT, a baby with this type of Pompe disease may not live past early childhood.

If your baby is diagnosed with a delay or low muscle tone, Vockley says, see a pediatric neurologist. They can evaluate your baby and decide whether they need a referral to a geneticist for genetic testing to look for Pompe disease.

While children with non-classic infantile-onset are less likely to get heart disease, he says, they should still be followed with regular echocardiograms.

 “With the right testing and treatment, children with Pompe disease, even with the most severe forms of Pompe disease, are living longer and having better quality of life than ever before,” Grant says

Late-onset Pompe disease may show during late childhood, the teen years, or adulthood. It's generally milder than infantile-onset disease. It's also less likely to involve your heart.

The main symptom is muscle weakness, especially in the torso and legs.

 “Sometimes, patients develop almost a waddling gait, and they may find it hard to stand after exercise, or even climbing stairs,” says Grant. You can have muscle weakness in your diaphragm too, which can lead to breathing problems.

Other symptoms may include:

  • Curved spine
  • Muscle aches and cramps
  • Headache
  • Fatigue

If you notice muscle weakness in your legs or torso (or in your child's) that didn’t exist before, check with your doctor or pediatrician. One study found this was the first symptom for 75% of people with late-onset Pompe disease.

Because Pompe disease is so rare (affecting about 1 in every 400,000 people in the U.S.), and because many other conditions have similar symptoms, getting a diagnosis can be tricky.  Research has shown it can take up to 13 years to get a diagnosis.

There's no cure for Pompe disease. But the sooner you start ERT, along with therapies for the other problems the disease can cause, the better you'll be able to manage your symptoms.  

 “Time is of the essence here,” Vockley says.