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Pompe Disease

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Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

Acid alpha-glucosidase deficiency (GAA)
Acid maltase deficiency/ Acid maltase deficiency disease
Alpha-1,4-glucosidase deficiency
AMD
Deficiency of alpha-glucosidase
GAA deficiency
Glycogen storage disease type II
Glycogenosis Type II
GSD II/ GSD2
Pompe's disease

ICD-10 Coding

E74.02, Pompe disease

Disorder Category

Lysosomal storage disorder

Screening

Abnormal Finding

Decreased GAA enzyme activity. Urine hexose tetrasaccharide (Hex4) may be elevated.

Tested By

N/A

Description

Pompe disease is one of the glycogen storage disorders (Type II) caused by a deficiency of the lysosomal acid alpha-glucosidase enzyme, resulting in the accumulation of glycogen. Pompe disease can be classified as either infantile-onset (IOPD) or late-onset (LOPD), which can be differentiated by the age of symptom onset and severity. If untreated, IOPD is rapidly progressive and typically fatal by 2 years of age, secondary to progressive left ventricular outflow obstruction and respiratory insufficiency. [Kishnani: 2006] The diagnosis of Pompe disease may be suspected based on an abnormal newborn screen (in states that test for Pompe disease), an elevated CK level, or elevated urinary oligosaccharides, and more specifically, tetrasaccharide.

Clinical Characteristics

With treatment, enzyme replacement therapy (ERT) is a treatment for Pompe disease that can delay progression of the disease, but it is not a cure. The response depends on many factors, including disease severity, time of therapy initiation, and cross-reactive immunogenic material (CRIM) status. In general, quality of life is improved and life expectancy prolonged. ERT is typically administered via IV infusion every 2 weeks lifelong. Some patients will develop IgG antibodies to ERT, 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 the severity of symptoms.
Without treatment of infantile-onset Pompe disease: [van: 2003]
  • Symptom onset <12 months of age
  • Muscle weakness and hypotonia
  • Hypertrophic cardiomyopathy
  • Respiratory distress
  • FTT/Feeding difficulties
Without treatment of late-onset Pompe disease: [Winkel: 2005]
  • Symptom onset 12 months of age
  • Proximal muscle weakness (particularly lower limbs)
  • Respiratory insufficiency secondary to diaphragm and intercostal muscle dysfunction
  • Fatigue/exercise intolerance
  • Difficulty chewing/swallowing

Incidence

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.

Inheritance

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%.

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and evaluate the infant if there are any concerns, such as muscle weakness, respiratory insufficiency, or feeding problems. Decreased GAA activity with current lab techniques may be reported with a pseudo-deficiency allele but notably does not actually cause Pompe disease.
  • Primary care clinicians may perform the following tests immediately while coordinating with specialists and awaiting the results of diagnostic testing: creatine kinase (CK), lactate dehydrogenase (LDH), ALT, AST, chest X-ray, EKG, and echocardiogram.

Confirming the Diagnosis

  • To confirm the diagnosis of Pompe disease, work with Newborn Screening Services (see NW providers [1]).
  • Follow-up testing will require confirmation by molecular genetic testing (GAA gene analysis) or measuring the acid alpha-glucosidase (GAA) enzyme activity measured in blood (leukocytes) or via muscle/skin biopsy. GAA activity will be decreased, in which <1% of activity is suggestive of IOPD and 2-40% enzyme activity suggests LOPD. [Scriver: 2001]
  • Genetic testing for biallelic variants in the GAA gene may also confirm a diagnosis and help predict disease severity. [Zampieri: 2011]

If the Diagnosis is Confirmed

  • For evaluation and ongoing collaborative management, consult Pediatric Neurology (see NW providers [0]).
  • Educate the family regarding signs, symptoms, and risk for recurrence.
  • Treatment with enzyme replacement therapy (ERT) should be initiated as soon as a diagnosis of IOPD is made and for LOPD once symptoms manifest. [Bali: 2012]
  • Support treatment as needed.

Resources

Information & Support

After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

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.

Acid Maltase Deficiency Association
Assists in funding research and promotes 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.

Tools

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 Nationwide (NW)

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.

Studies

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

PubMed search for articles about Pompe disease in children

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; last update/revision: March 2024
Current Authors and Reviewers:
Author: Brian J. Shayota, MD, MPH
Reviewer: Nancy C. Rose, MD
Authoring history
2023: update: Brian J. Shayota, MD, MPHA
2021: first version: Brian J. Shayota, MD, MPHA
AAuthor; CAContributing Author; SASenior Author; RReviewer

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

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

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

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

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.

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

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