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Why is Early Diagnosis Important?

Pompe disease is a progressive, neuromuscular disease. While patients may not show symptoms for many years (sometimes even decades), the disease is present and active at birth. Multiple trials have shown that treatment with enzyme replacement therapy (ERT) can significantly alter the natural history of Pompe disease in patients. In short, it saves lives.

However, studies have also shown that a critical component of a successful outcome with ERT is the initiation of treatment before irreversible damage has occurred. In an Editorial titled “Early is better? A new algorithim for early diagnosis in Late Onset Pompe Disease (LOPD),“ Drs. Antonio Toscano and Olimpia Musumeci stated: “In LOPD, the efficacy of ERT has been demonstrated but with less prominent efficacy when compared to the infantile cases. In fact, it has been shown that ERT may improve or stabilize motor performances and respiratory function in at least 2/3 of treated patients. Some studies reported that an early start of therapy may maximize ERT efficacy, suggesting that, in LOPD, an earlier diagnosis has to become the key point in patients’ management” (https://amda-pompe.org/wp-content/uploads/2020/06/Early_is_better.pdf).

The importance of early diagnosis is even more critical in Infantile-Onset patients. In fact, in “Very Early Treatment for Infantile-Onset Pompe Disease Contributes to Better Outcomes,” the authors reported “we found that starting ERT even a few days earlier was associated with better biochemical responses and developmental outcomes” (https://amda-pompe.org/wp-content/uploads/2020/06/Very_Early_Treatment_for_Infantile-Onset_Pompe_Disease_Contributes_to_Better_Outcomes.pdf). The key to early initiation of treatment is early diagnosis. Without a diagnosis it is impossible to start treatment before irreversible damage has occurred. However, achieving an early diagnosis is complicated by the fact that symptoms of Pompe can occur at any age, and are often difficult to detect at first.

How to Diagnose Pompe Disease

There are several ways that Pompe disease can be diagnosed. In many cases, after initial diagnosis by one method, confirmation by a second method is required.

  • Enzyme Activity Testing is used to evaluate a patient’s GAA enzyme level. GAA is the abbreviation for the enzyme that Pompe patients do not produce in sufficient quantities (i.e. they are deficient in). Pompe patients have enzyme levels that range from <1% to 40%. If an abnormal (i.e. low) level of GAA activity is found, then a confirmatory test using a different sample or one of the methods listed below will be used to confirm a diagnosis of Pompe disease.
    – Whole Blood, Dried Blood Spot, and Lymphocyte Testing are all methods by which a patient’s GAA enzyme level can be tested using blood.
    – Fibroblasts, which are created from cultured skin biopsies, are another way to measure a patient’s GAA activity. Collecting a skin biopsy is a minimally invasive process that involves removing a very small piece of the patient’s skin.
    – Muscle biopsies can also be used to collect samples to test for enzyme activity in patients.
  • DNA Analysis is another method to diagnose Pompe disease. Through this process, the gene that causes Pompe disease is examined to identify the patient’s mutations. Blood or spit can be used to collect a patient’s DNA for this testing method; however, the spit method is only available in the United States at present.
  • Muscle Tissue Pathology, which is obtained by a muscle biopsy, can also be used to diagnose Pompe disease. This is done by a pathologist who examines the tissue to see if there are vacuoles that stain positively for Pompe disease. However, the absence of vacuoles does not rule out Pompe disease.

For country/region specific information on who to contact regarding testing for Pompe disease, please check out the following links:

“Differential” Diagnosis

Or, what other disease does Pompe share symptoms with?

The first symptoms of Pompe disease can vary greatly from patient to patient, which is one of the reasons it can be so difficult to diagnose. The other reason it can be difficult to diagnose is that Pompe disease shares symptoms with many other diseases.

Infantile-Onset Pompe disease shares symptoms with the following diseases:
  • Werdnig-Hoffman disease: poor muscle tone/muscle weakness, feeding difficulties, high CK levels
  • Danon disease: heart disease, muscle damage, glycogen accumulation, high CK levels
  • Glycogen Storage disease IIIA&IV: poor muscle tone/muscle weakness, enlarged heart, high CK levels, enlarged liver
  • Endocardial Fibroelastosis: feeding difficulties, enlarged heart, respiratory difficulties
Late-Onset Pompe disease shares symptoms with the following diseases:
  • FSHD (Facioscapulohumeral muscular dystrophy): slowly progressive muscle weakness
  • Polymyositis: progressive muscle weakness, difficulty swallowing, high CK levels
  • Limb-girdle Muscular Dystrophy: progressive muscle weakness in hips, legs, or shoulders, high CK levels, abnormal walk/gait
  • Duchenne-Becker Muscular Dystrophy: progressive muscle weakness, starting in the trunk of the body, respiratory difficulties, difficulty walking, high CK levels
  • Glycogen Storage Disease V: High CK levels, difficulty participating in physical activities

If the above diseases are suspected, it is easy to test for Pompe as well. The worst that would happen is that Pompe would be ruled out, but the best outcome would be that an otherwise mis-diagnosed or undiagnosed patient will be diagnosed and can begin treatment.

How You Can Help

Because Pompe disease is rare, most people have never heard of it. How can you recognize and diagnose a disease if you don’t know if exists? But we can all help to change that! Let’s show the world that “Together We Are Strong” and spread the word about the importance of Early Diagnosis for Pompe and how to recognize its symptoms!

Informational Flyers have been created and translated into multiple languages for the patient community to use. Print some out and share, or share this page and we will get the word out that Early Diagnosis is Key!