Pompe Disease

Other Names

Acid maltase deficiency

Acid maltase deficiency disease

Alpha-1,4-glucosidase deficiency


Deficiency of alpha-glucosidase

GAA deficiency

Glycogen storage disease type II

Glycogenosis Type II



Pompe's disease

Diagnosis Coding

E74.02, Pompe disease

Disorder Category

A lysosomal storage disorder



Decreased GAA enzyme activity

Tested By



Pompe disease is one of the glycogen storage disorders (Type II) caused by a deficiency of the lysosomal acid alpha-glucosidase enzyme, although clinically, it is very distinct from the other glycogen storage disorders. Pompe disease can be classified as either Infantile-Onset Pompe disease (IOPD) or Late-Onset Pompe disease (LOPD), which can be differentiated by the age of symptom onset and severity.

In IOPD, symptoms are typically present within the first few months of life and no later than 12 months. Characteristic symptoms may include generalized weakness, hypotonia, cardiomyopathy, and respiratory distress. [van: 2003] If untreated, this form is typically fatal by 2 years of age secondary to progressive left ventricular outflow obstruction and respiratory insufficiency. [Kishnani: 2006].

LOPD is clinically much more variable with symptom onset after 12 months of age and possibly not until well into adulthood. Characteristic symptoms include progressive muscle weakness, exercise intolerance, respiratory insufficiency secondary to diaphragm and intercostal muscle dysfunction, scoliosis, and chewing difficulties. [Winkel: 2005]

The diagnosis of Pompe disease may be suspected based on an abnormal Newborn Screen (in the states that test for it), an elevated CK level, or elevated urinary oligosaccharides and more specifically, tetrasaccharide. Confirmation can be made with acid alpha-glucosidase (GAA) enzyme activity, in which <1% of activity is suggestive of IOPD and 2-40% enzyme activity suggest LOPD. [Scriver: 2001] Genetic testing for biallelic variants in the GAA gene may also be done to confirm a diagnosis and help predict disease severity [Zampieri: 2011]. Treatment with enzyme replacement therapy (ERT) should be initiated as soon as a diagnosis of IOPD is made, and for LOPD once symptoms manifest. Determination of cross-reactive immunologic material (CRIM) status will also help determine the risk for developing anti-rhGAA antibodies to the ERT and require a modified therapy protocol [Bali: 2012]. Treatment improves symptoms, prolongs life expectancy, and changes clinical presentation—but is not a cure.


Pompe disease affects about 1:40,000 people in the United States. The incidence varies among ethnic groups and is more common in African Americans and individuals from southern China and Taiwan.


Mutations in the GAA gene cause Pompe disease, which is inherited in an autosomal recessive pattern. Therefore, the recurrence risk for parents of an affected child is 25%.

Prenatal Testing

Supportive Testing
  • Newborn Screening (not routine in all states) analysis of acid alpha-glucosidase (GAA) enzyme activity on dried blood spots
  • Elevated serum creatine kinase (CK) in nearly all with IOPD and some with LOPD
  • Elevated tetrasaccharide on urinary oligosaccharides is highly sensitive for IOPD but can be seen in other glycogen storage diseases as well.

Other Testing

Diagnostic Testing
  • Decreased acid alpha-glucosidase (GAA) enzyme activity measured in blood (leukocytes) or via muscle/skin biopsy.
  • Genetic testing for variants in the GAA gene. It can also be done prenatally by amniocentesis or CVS, ideally when the gene variant in the family is already known. The genotype may also correlate with disease severity, including age of onset, rate of progression, and CRIM status.

Clinical Characteristics

IOPD (without treatment):
  • Symptom onset <12 months of age
  • Muscle weakness and hypotonia
  • Hypertrophic cardiomyopathy
  • Respiratory distress
  • FTT/Feeding difficulties

LOPD (without treatment):
  • Symptom onset >12 months of age
  • Proximal muscle weakness (particularly lower limbs)
  • Respiratory insufficiency
  • Fatigue/Exercise intolerance
  • Difficulty chewing/swallowing
With treatment:
Enzyme replacement therapy (ERT) is a treatment that can delay progression of the disease, but it is not a cure. Response depends on many factors including disease severity, progression at time of therapy initiation, and CRIM status. In general, quality of life is improved and life expectancy prolonged. Lumizyme and Myozyme are both FDA-approved treatments in the US. ERT is typically administered via IV infusion every two weeks lifelong. Some patients will develop IgG antibodies to ERT, particularly those found to be CRIM negative, which has been associated with poor response to treatment and may require immune tolerance induction. [Messinger: 2012]

Gene therapy trials are in progress but are currently targeted only towards adults. Supportive Treatment: May include physical therapy, occupational therapy, speech therapy, feeding tubes, and mechanical ventilation depending on severity of symptoms.

Follow-up Testing after Positive Screen

Positive screening results need confirmation by molecular genetic testing (GAA gene analysis) or measuring the GAA activity.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and risk recurrence.
  • Support treatment management as needed.
  • Prescribe supportive therapies as needed.

Specialty Care Collaboration

Initial consultation and ongoing collaboration with the following service(s): Pediatric Genetics (see NV providers [4]). Genetic counseling for the family.


Information & Support

For Professionals

Pompe Disease (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

For Parents and Patients

Pompe Disease - Information for Parents (newbornscreening.info)
Very detailed information for families, including description, causes, outcomes, genetic testing, incidence, and more; from the Screening, Technology And Research in Genetics Project, begun by the Hawaii Department of Health and now maintained by the Western States Regional Genetics Network.

Pompe Disease (MedlinePlusGenetics)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Pompe Community (Sanofi Genzyme)
Information for patients, caregivers, and health care providers about Pompe disease.

Acid Maltase Deficiency Association
The Acid Maltase Deficiency Association formed to assist in funding research and to promote public awareness of Acid Maltase Deficiency, also known as Pompe’s Disease.

Acid Maltase Deficiency (Pompe disease) (MDA)
Provides information about symptoms, causes, and progression of acid maltase deficiency; Muscular Dystrophy Association.

Pompe Disease (NORD)
Information for families, including synonyms, signs & symptoms, causes, affected populations, related disorders, diagnosis, therapies (both standard and investigational), and support organizations; from the National Organization of Rare Disorders.


ACT Sheet for Pompe Disease (ACMG) (PDF Document 542 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for Pompe Disease (ACMG) (PDF Document 404 KB)
A resource for clinicians to help confirm diagnosis; American College of Medical Genetics.

Services for Patients & Families in Nevada (NV)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.


Clinical Trials in Pompe Disease (clinicaltrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Helpful Articles

Kohler L, Puertollano R, Raben N.
Pompe Disease: From Basic Science to Therapy.
Neurotherapeutics. 2018;15(4):928-942. PubMed abstract / Full Text

Dasouki M, Jawdat O, Almadhoun O, Pasnoor M, McVey AL, Abuzinadah A, Herbelin L, Barohn RJ, Dimachkie MM.
Pompe disease: literature review and case series.
Neurol Clin. 2014;32(3):751-76, ix. PubMed abstract / Full Text

Authors & Reviewers

Initial publication: June 2021
Current Authors and Reviewers:
Author: Brian J. Shayota, MD, MPH

Page Bibliography

Bali DS, Goldstein JL, Banugaria S, Dai J, Mackey J, Rehder C, Kishnani PS.
Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience.
Am J Med Genet C Semin Med Genet. 2012;160C(1):40-9. PubMed abstract / Full Text

Kishnani PS, Hwu WL, 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(5):671-676. PubMed abstract

Messinger YH, Mendelsohn NJ, Rhead W, Dimmock D, Hershkovitz E, Champion M, Jones SA, Olson R, White A, Wells C, Bali D, Case LE, Young SP, Rosenberg AS, Kishnani PS.
Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease.
Genet Med. 2012;14(1):135-42. PubMed abstract / Full Text

Scriver CR, Beaudet A, Sly WS, Valle D, eds.
The Metabolic and Molecular Bases of Inherited Disease.
New York, NY: McGraw-Hill; 2001.
Chapter by Hirschhorn R, Reuser AJ. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. 389-420.

Winkel LP, Hagemans ML, van Doorn PA, Loonen MC, Hop WJ, Reuser AJ, van der Ploeg AT.
The natural course of non-classic Pompe's disease; a review of 225 published cases.
J Neurol. 2005;252(8):875-84. PubMed abstract

Zampieri S, Buratti E, Dominissini S, Montalvo AL, Pittis MG, Bembi B, Dardis A.
Splicing mutations in glycogen-storage disease type II: evaluation of the full spectrum of mutations and their relation to patients' phenotypes.
Eur J Hum Genet. 2011;19(4):422-31. PubMed abstract / Full Text

van den Hout HM, Hop W, van Diggelen OP, Smeitink JA, Smit GP, Poll-The BT, Bakker HD, Loonen MC, de Klerk JB, Reuser AJ, van der Ploeg AT.
The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature.
Pediatrics. 2003;112(2):332-40. PubMed abstract