Diagnostic Pathway

Pompe disease is rare and often presents with a cluster of non-specific signs and symptoms which may contribute to significant diagnostic delays across all patient populations. Although the clinical paths to diagnosis are variable,[1]  the process generally involves:

  1. Clinical evaluation of presenting symptoms by a gateway physician
  2. Referral to a specialist for further clinical investigation, including additional lab or clinical tests
  3. Confirmatory testing

Details of this process vary between infants and older patients because of the different clinical manifestations and rates of disease progression. However, because the disease is so rapidly progressive, clinical decline during this period of time can be profound.[2] The diagnostic algorithms presented below may help clarify the complex diagnostic process for Pompe disease.

Diagnostic Algorithm for Infants with Pompe Disease

Details for each stage are provided below:

1. Clinical evaluation of presenting clinical manifestations

  • An infant may present to a pediatrician, with parents concerned by signs of hypotonia, developmental delays, and/or feeding difficulties.
  • An infant may be seen by an emergency room physician because of cardiac and/or respiratory distress.

Get full details on signs in infants

2. Referral to specialists for further investigation

  • Because of the predominance of cardiac involvement in infants, the initial referral is often to a pediatric cardiologist. Chest x-rays and ECGs usually reveal cardiomegaly and other cardiac complications.
  • Additional tests may uncover respiratory insufficiency, elevated creatine kinase levels, and other signs suggestive of Pompe disease.

Find out more about these and other useful assessments

3. Confirmatory tests

  • Once a clinical suspicion is raised and tentative diagnosis is made, Pompe disease can be quickly and easily confirmed by an enzyme assay.
    Get details on tests for confirming a diagnosis
  • Upon a conclusive diagnosis, genetic and family testing may also be recommended.

Diagnostic Algorithm for Older Patients

This illustration provides an overview of the diagnostic algorithm for identifying Pompe disease in children and adults.[3]  Additional details for each stage are provided below.

 

AANEM Practice Topic: Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle & Nerve 2009;40:149-160. With permission.

1. Clinical evaluation of presenting symptoms

  • Patients often present to their primary care physician, with complaints about their physical abilities—general muscle weakness, frequent falls, difficulty running, walking, climbing stairs or standing up.
  • Some patients may present with respiratory symptoms, most commonly at night or when lying down, and often resulting in morning headaches and daytime fatigue.
  • Questions about the patient’s earlier medical history may uncover childhood difficulties that can, in retrospect, be seen as early signs of this progressive disease.[4]

Get full details on signs and symptoms in children and adults

2. Referral to specialists for further investigation

  • Because symptoms can be non-specific and sometimes seemingly mundane, the patient may make multiple visits to the primary care physician and it may take some time before specialists are involved.
  • If musculoskeletal symptoms predominate, the patient may see a neurologist or neuromuscular specialist. Electrophysiology and other tests usually reveal myopathy and compromised motor function.
  • If respiratory symptoms predominate, the patient may see a pulmonologist or respiratory specialist, who may identify reduced respiratory function and other respiratory compromise.

Find out more about these and other useful assessments

3. Confirmatory tests

  • Once a clinical suspicion is raised and tentative diagnosis made, Pompe disease can be quickly and easily confirmed through an enzyme assay.
    Get details on tests for confirming a diagnosis
  • Upon a conclusive diagnosis, genetic testing and family screening may also be recommended.

Take Note: A Debilitating Delay

The signs of Pompe disease in children, adolescents, and adults are generally not as immediately life-threatening as they are in infants. The average diagnostic delay is 7 years.[4] Over this time, the disease may progress slowly but relentlessly, causing physical disability and ultimately having life-threatening impact.

References

  1. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8:267-88.
  2. Kishnani PS, Hwu W-L, Mandel H, Nicolino M, Yong F, Corzo D. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; 148:671-676.
  3. Diagnostic criteria for late-onset (childhood and adult) Pompe disease. American Association of Neuromuscular & Electrodiagnostic Medicine. Muscle Nerve. 2009;40(1):149-160.
  4. Hagemans ML, Winkel LP, Van Doorn PA, et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 2006; 128:671-7.
  5. Kishnani PS, Hwu W-L, Mandel H, Nicolino M, Yong F, Corzo D. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; 148:671-676.

Find Diagnostic Labs

Get a list of laboratories that can perform enzyme assays and other useful tests to aid in the diagnosis of Pompe disease.

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