Pompe Disease Clinical and Research Program
Dedicated to the holistic, bench-to-bedside approach to diagnosis, management, and treatment of individuals with Pompe disease.
What is Pompe? (pronounced "pom-pay")
Pompe disease is an inherited and often fatal disorder caused by the deficiency of acid alpha-glucosidase (GAA), an enzyme needed to break down glycogen (sugar that is stored for energy) in specialized structures in our body, called lysosomes. Patients with Pompe disease have little or no GAA enzyme activity and cannot break down glycogen. The excess glycogen accumulates and is stored in the heart, skeletal muscle and other tissues, causing the progressive symptoms of Pompe disease.
Other names for Pompe disease:
- Acid Maltase Deficiency
- Glycogen Storage Disease Type II
- Glycogenosis Type II
- Acid alpha-Glucosidase Deficiency
- Lysosomal alpha-Glucosidase Deficiency
We've come a long way in our understanding of Pompe disease, but there remains a great deal of unfinished work. I am humbled and honored to be a part of this process.
--Priya Kishnani, MD
What are the symptoms?
Pompe disease is classified based on age of onset, severity, and rate of progression.
Classic infantile-onset Pompe disease (symptoms present in the first month of life)
- Hypotonia or generalized muscle weakness
- Delayed gross motor development
- Feeding difficulties
- Failure to thrive
- Respiratory distress
- Hearing difficulties
- Normal intelligence
Without treatment with enzyme replacement therapy (ERT), there is progressive cardiomegaly (enlarged heart) or hypertrophic cardiomyopathy (thickened heart muscle), which ultimately results in cardiopulmonary insufficiency.
Late onset Pompe disease (symptoms present in childhood or later)
- Progressive muscle weakness mostly affecting lower limbs with positive Gower sign
- Shortness of breath, exercise intolerance, respiratory insufficiency, and increased respiratory infections
- Sleep apnea
- Hyperlordosis (swayback) and/or scoliosis (curvature of the spine)
- Hepatomegaly (liver enlargement)
- Macroglossia (tongue enlargement) with difficulty chewing and swallowing
- Decreased deep tendon reflexes
- Joint contractures
- Cardiac hypertrophy (thickened heart muscle)
How is Pompe disease diagnosed?
GAA activity assay for the diagnosis of Pompe disease can be performed in various tissues. Glycogen content can be measured in muscle biopsy samples to support the diagnosis. Prenatal testing is available on CVS samples and cultured amniocytes. Enzyme testing is not appropriate for carrier testing. Carrier testing and prenatal testing are available if the familial mutations have been previously identified.
The following tests are currently available:
- Enzyme assays for acid alpha-glucosidase (GAA) in blood, cultured skin fibroblasts, muscle, and cultured amniocytes, and chorionic villi
- GAA gene sequencing
- Urinary hexose tetrasaccharide (Hex4), a marker of disease burden in Pompe disease that can be used to monitor patients with Pompe disease and as a second tier diagnostic test
- Analysis of Cross Reactive Immunological Material (CRIM status)
- Pompe Disease Test Request Form
- Sequencing Test Request Form via the Duke Molecular Diagnostics Laboratory
Biochemical Genetics Laboratory
Glycogen Storage Disease Laboratory
DUHS Clinical Laboratories
801 Capitola Drive, Suite 6
Durham, NC 27713
For me, as a doctor, diagnosing the disease wasn't enough, I wanted to treat it.
--Y.T. Chen, MD, PhD
The Duke Pompe Disease Clinical and Research Program follows a systematic and multidisciplinary management and treatment of patients with Pompe disease across the clinical spectrum, as recommended in the Pompe Disease Diagnosis and Management Guidelines. Our physicians and staff proudly serve a broad, international patient population, providing clinical care and consultation to individuals with Pompe disease and their attending physicians, worldwide.
The Duke Pompe Disease Clinical and Research Program offers infusions with enzyme replacement therapy (ERT)—a treatment that provides a genetically engineered form of the GAA enzyme to replace the deficient or absent enzyme in the patient’s blood. The concept of ERT was developed by DUMC researchers, then clinical trials at Duke demonstrated benefit for patients with infantile Pompe—reduction of glycogen storage, decreased heart size and normal function, and improved muscle tone. The drug alglucosidase alfa in the form of Myozyme© received FDA approval 4/28/2006 for infantile Pompe, followed by FDA approval of Lumizyme© in 2010 for children and adults with late-onset Pompe disease.
We uphold an ongoing commitment to individuals with Pompe disease and their families. Through translational research initiatives, we continually strive to achieve earlier diagnoses, to enhance therapy and treatment methods, to improve patient and family quality of life, and to maximize day-to-day abilities for individuals living with Pompe disease. Our team coordinates several ongoing clinical trials and research initiatives in order to:
- Increase medical knowledge in order to promote early diagnosis and treatment
- Understand the natural history and progression of symptoms across the disease spectrum
- Determine the effectiveness of ERT with attention to multisystemic disease manifestations
- Develop biomarkers as non-invasive surveillance of disease
- Evaluate the role of immune response in Pompe disease and explore preventative measures
- Study the effects of immune modulation in individuals with high antibody titers
- Identify the role of exercise and nutrition in Pompe disease
- Examine improvements following respiratory muscle strength training (RMST)
- Establish new and innovative treatment strategies for Pompe disease
GAA Mutation Database
I am the first adult to receive Myozyme. You would not be talking to me if it wasn't for this.
--Abby, North Carolina
We were told we needed to talk to the experts, and they're at Duke.
--Maddison's Mom, North Carolina
I have a normal life--I'm married with two girls. I fully expect to watch my grandchildren grow up.
--Robert, North Carolina
We were impressed with [Duke's] knowledge of Pompe and switched things immediately.
--Haley's Mom, Virginia
Thanks to Dr. Kishnani and her outstanding colleagues, our son Ryan's future is now much more promising than we faced a year ago. We are truly thankful for the opportunity that these dedicated professionals have given our son.
--Ryan's Dad, Illinois
I would like to thank Duke for its pioneering research on Pompe disease. Soon after coming to Durham, I learned that Duke Hospital, because of the research done by Dr. Y.T. Chen and his team, had been a pioneer in developing enzyme infusion treatment. Even in my limited knowledge of this work, I have been blown away by the brilliance of the research and the impact it could have on patients like my daughter.
--Nandita's father, Massachusetts
Save the Date: 5th Annual Late-Onset Pompe Disease Patient Meeting
The Duke Pompe Disease Clinical and Research Program at Duke University Medical Center, in partnership with the United Pompe Foundation, plans to host the 5th Annual Late-Onset Pompe Disease (LOPD) Patient Meeting, April 29-30, 2016. The meeting is supported by educational grants from Genzyme Corp., BioMarin Pharmaceutical, Inc. and Amicus therapeutics.
- The new era of Pompe disease: Advances in the detection, understanding of phenotypic spectrum, pathophysiology and management [PDF, 277KB]
- Generating color-coded anatomic muscle maps for correlation of quantitative MRI analysis with clinical examination in neuromuscular disorders [PDF, 623KB]
- Oropharyngeal dysphagia may occur in late-onset Pompe disease, implicating bulbar muscle involvement [PDF, 149KB]
- The impact of antibodies in late-onset Pompe disease: A case series and literature review [PDF, 823KB]
- Pompe Disease Diagnosis and Management
Medical Genetics Team
|Priya S. Kishnani, MD||Division Chief, Geneticist|
|Dwight Koeberl, MD, PhD||Geneticist|
|Marie McDonald, MD, MB, BCh||Geneticist|
|Stephanie Wechsler, MD||Geneticist & Cardiologist|
|Y.T. Chen, MD, PhD||Geneticist|
|Deeksha Bali, PhD||Laboratory Director|
|Sarah Young, PhD||Laboratory Director|
|Jennifer Goldstein, PhD||Clinical Research Coordinator|
|Stephanie DeArmey, MHS, PA-C||Physician Assistant|
|Crista Walters, RN||Nurse Practitioner|
|Stephanie Austin, MS||Genetic Counselor|
|Lauren Bailey, MS||Genetic Counselor|
|Katie Berrier, MS||Genetic Counselor|
|Surekha Pandyal, RD, LDN||Metabolic Dietician|
|Laura Case, DPT, PCS||Physical Therapist|
|Lisa Hobson-Webb, MD||Neurologist|
|Harrison Jones, PhD||Speech Pathologist|
|Richard Kravitz, MD||Pulmonologist|
|Jennifer Li, MD||Cardiologist|
|Grace Prakalapakorn, MD||Opthalmologist|
|Eileen Raynor, MD||Otolaryngologist|
|Yul Reinstein, MD||Gastroenterologist|
|Henry Rice, MD||General Surgeon|
|Allison Ross, MD||Anesthesiologist|
|Edward Smith, MD||Neurologist|
|Gail Spiridigliozzi, PhD||Psychologist|
Durham, NC 27705
Hours: Mondays, 8:00 am - 3:00 pm
Patients may be seen in consultation by additional sub-specialties in other outpatient clinics:
2301 Erwin Road
Durham, NC 27710
- Medical Genetics Home
- Division of Medical Genetics
(Duke School of Medicine)
- Clinical Genetics Services
- Pompe Disease Clinical and Research Program
- Comprehensive Down Syndrome Program
- Down Syndrome Disintegative Disorder Clinic
- Glycogen Storage Disease Clinical and Research Program
- General Genetics Clinic
- Metabolic Clinic
- Autism/Medical Genetics Clinic
- Cardiovascular Genetics Clinic
- Fragile X Syndrome Clinic
- Marfan/Connective Tissue Disorder Genetics Clinic
- 22q11 Deletion Syndrome Clinic
2016 Late-Onset Pompe Disease Patient Meeting
April 29-30, 2016
2016 Infantile Onset Pompe Disease Patient Meeting
August 2016 - TBD
- Targeted Gene Therapy Enhances Treatment for Pompe Disease
(Human Gene Therapy)
- Cancer Drugs Help the Hardest Cases of Pompe Disease
- Duke Research Leads to "Extraordinary Measures" Film
- Pompe Disease: The Story Behind the Movie
- Hollywood vs. Real Life: Duke Scientist Developed Pompe Disease Drug
- WRAL Highlights Duke's Pompe Research
(Inside Duke Medicine)
- News 14 Features Duke's Pompe Research
(Inside Duke Medicine)
- The Making of a Miracle
- New Movie Sheds Light on Disease
- Duke Research, Hollywood Glory
- Breakthrough Treatment for Pompe Disease
- Celebrating a Victory Over Pompe Disease
(Inside Duke Medicine)
- Duke University Starts Clinical Trials
- The Myozome Miracle
(Inside Duke Medicine)
- Pompe Disease: A Killer Yields to Modern Medicine
- Living With Pompe Disease
(Duke Clinical Research Institute)
- New Treatment Helps Children with Pompe Disease Live Longer
Timeline of Myozome Treatment for Pompe Disease
Duke genetically engineers cell lines to overproduce the necessary enzyme
Duke established that the enzyme works in cultured cells from Pompe patients
Duke established that the enzyme works in vivo in an animal model; Japanese quail injected with enzyme overcome muscle weakness. One flies.
Duke obtains FDA Orphan Drug Designation for Pompe therapy.
The British-based Taiwanese biotech company Synpac obtains license from Duke to produce enzyme for clinical trials.
First clinical trial of enzyme replacement therapy in humans begins in Duke's General Clinical Research Center (GCRC). Y.T. Chen, M.D., Ph.D., is principal investigator.
Biotech firm Genzyme obtains license from Synpac to produce enzyme.
Phase II clinical trial begins with 8 patients (5 treated at Duke). Priya Kishnani, M.D., is principal investigator.
Genzyme compares four different methods for producing enzyme and chooses the modified Chinese hamster ovary cell-line product using an existing Genzyme cell line.
Phase III clinical trial for patients with infantile-onset Pompe disease. Priya Kishnani is the principal investigator.
Clinical trials begun for patients with late-onset Pompe disease
Broad label market approval for Myozyme in Europe (March 29) and in U.S. (April 28). Guidelines published for diagnosis and management of Pompe Disease in
Genetics in Medicine.
- Acid Maltase Deficiency Association (AMDA)
- Genetic Alliance
- International Pompe Association (IPA)
- Muscular Dystrophy Association (MDA)
- National Organization for Rare Diseases (NORD)
- Pompe Community
- Pompe InCommon
- Rare Diseases Clinical Research Network (RDCRN)
- United Pompe Foundation (UPF)
- A Wish With Wings
- Chai Lifeline
- Children's Miracle Network
- Children Living with Inherited Metabolic Diseases (CLIMB)
- Contact A Family
- First Hand Foundation
- Helping Hands Loving Hearts
- Make a Wish Foundation
- Make a Wish Foundation, International
- Starlight Foundation
- American Psychological Association (APA)
- APA Help Center
- Chai Lifeline
- National Society of Genetic Counselors
- Pompe Disease Diagnosis and Management Guidelines
- Glycogen Storage Disease Type II (Pompe)
- Genzyme Corporation
- Center for Drug Evaluation and Research (CDER) Handbook
- From Test Tube to Patient (FDA)
- Health on the Net Foundation
- National Center of Biotechnology Information
- Office of Rare Diseases Research (ORDR)
- Division of Medical Genetics
(School of Medicine)
- Clinical Trials
- Download a list of publications written by members of the Duke Pompe Disease Clinical and Research Program.
There are many ways you can help in the fight against Pompe disease. Concerned individuals, companies and organizations have made it possible for Duke University to continue its research efforts and programs to aid those with Pompe disease and their families. If you would like to make a contribution, please visit our online form and specify Pompe Disease Research in the Gift Designation section.