Paediatrics CME ACCREDITED Watch Time: 35 mins

touchEXPERT OPINIONS Pompe disease: Expanding manifestations and evolving management

Watch leading experts discuss recent developments in Pompe disease, including refined understanding of phenotypes and multisystem clinical manifestations emerging in the era of enzyme replacement therapy (ERT). The impact on paediatric patients and their caregivers is also explored, alongside approaches to further optimize multidisciplinary management of Pompe disease.

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Prof. Damara Ortiz
Clinical Geneticist and Assistant Professor of Pediatrics, University of Pittsburgh Medical Center Children’s Hospital, Pittsburgh, PA, USA
How has successful ERT treatment in IOPD changed the phenotype?

Prof. Damara Ortiz provides an update on how prolonged survival in patients receiving enzyme replacement therapy (ERT) has altered the infantile-onset Pompe disease (IOPD) phenotype. She also considers the emerging clinical implications for effective clinical management strategies arising from improved understanding of IOPD as a multisystem disorder.

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Interview Questions

In this interview, Prof. Damara Ortiz answers the following questions:

  • What is IOPD?
  • How does IOPD impact paediatric patients and their caregivers?
  • How is IOPD diagnosed?
  • How is IOPD treated?
  • With ERT prolonging survival, what have we learned about the IOPD phenotype?
About Prof. Damara Ortiz

Prof. Damara Ortiz is currently a Clinical Geneticist and Assistant Professor of Pediatrics at UPMC Children’s Hospital, and is actively involved in the clinical management of a variety of complex and rare metabolic conditions, including Pompe disease. Prof. Ortiz’s clinical work also encompasses cutting-edge research and transplantation to improve the lives of patients and their families. read more

Prof. Ortiz is Clinical Director of UPMC’s Lysosomal Storage Disorder Program and is the Principal Investigator for several lysosomal storage disorder clinical trials and patient registries.  Prof. Ortiz is Program Director of the Clinical Genetics and Genomics Residency Program where she created a didactic and board-reviewed curriculum for our trainees (Clinical Genetics and Genomics, Clinical Biochemical, Laboratory Genetics and Genomics). Actively involved in teaching, Prof Ortiz contributes to the UPMC Genetic Counselor Training program, serving as Medical Director. Prof. Ortiz has published book chapters and peer-reviewed papers in the field of lysosomal storage disorders.

Prof. Damara Ortiz discloses: Grants/research support from Amicus, BioMarin, Sanofi-Genzyme and Takeda. Consultant/advisory boards for Amicus and Sanofi-Genzyme.

Prof. Virginia Kimonis
Clinician Scientist and Professor of Genetics and Genomic Medicine, UC Irvine, CA, USA
Examining the expanding clinical manifestations of LOPD

Prof. Virginia Kimonis talks us through how improved clinical management and outcomes in the era of ERT has expanded our understanding of the phenotypic spectrum in LOPD. Now considered a multisystem disorder, Prof. Kimonis shares clinical insights on how the expanded LOPD phenotype may impact the treatment landscape and facilitate individualized care for patients living with LOPD.

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Interview Questions

In this interview, Prof. Virginia Kimonis answers the following questions:

  • What is LOPD?
  • How is LOPD diagnosed?
  • Is there a picture of best practice in LOPD, and what does it currently look like?
  • How has the advent of ERT altered the LOPD landscape?
  • How are recent developments in LOPD impacting clinical practice?
About Prof. Virginia Kimonis

Prof. Virginia Kimonis is currently a Clinician Scientist and tenured professor in the Division of Genetics and Genomic Medicine in the Department of Pediatrics at UC Irvine and Children’s Hospital, Orange County. After undertaking her residency in Pediatrics at Massachusetts General Hospital, Boston, she completed her fellowship training in Clinical and Biochemical Genetics at the National Institutes of Health, Johns Hopkins and Washington DC Children’s Hospital. read more

Prof. Kimonis specializes in the diagnosis and management of children and adults with neuromuscular, neurodegenerative and other complex disorders. She is actively involved in clinical and laboratory research, focussing on rare disorders including lysosomal storage diseases. Prof. Kimonis developed the UCI Lysosomal Disease Program, encompassing key trials and a registry study in a large cohort of patients with Pompe disease, publishing extensively in the field.

Prof. Virginia Kimonis discloses: Grants/research support from Sanofi-Genzyme. Consultant/advisory boards for Sanofi-Genzyme.

Prof. Loren Pena
Clinical Geneticist and Associate Professor of Pediatrics, UC Department of Pediatrics, Cincinnati, OH, USA
Improving skeletal muscle targeting with new approaches to ERT

Prof. Loren Pena summarizes the current unmet needs surrounding existing enzyme replacement therapies (ERT) in Pompe disease, and provides an overview of new and emerging clinical management strategies, including gene therapy. She also reflects on how these latest developments may impact future clinical practice.

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Interview Questions

In this interview, Prof. Loren Pena answers the following questions:

  • What are the current limitations of ERT?
  • How can we improve the effectiveness of rhGAA ERT in Pompe disease?
  • Could targeted gene therapy be a viable treatment option in future?
  • How might the latest developments in treatment options for IOPD and LOPD impact future clinical practice?
About Prof. Loren Pena

Prof. Loren Pena is currently Associate Professor in the UC Department of Pediatrics, Division of Human Genetics, Cincinnati, USA. After earning her medical degree from The Feinberg School of Medicine, Northwestern University, Chicago, she went on to complete residencies in both Pediatrics and Clinical Genetics at The University of Chicago. She obtained her PhD in Cancer Genetics and completed the NIH-supported Medical Scientist Training Program. read more

She was an investigator in the Undiagnosed Diseases Network at the Duke University site, and was part of the team that described new genes involved in human disease, such as ASXL2= and IRF2BPL.  She is also a clinical trialist who is interested in innovative approaches to treat rare disorders, particularly neurological conditions. She has been the principal investigator for several studies that utilize DNA and RNA-based methods to treat inherited conditions. Prof. Pena has published extensively in the field of rare and heritable diseases.

Prof. Loren Pena discloses: Grants/research support from Shire and Takeda. Consultant/advisory boards for Avexis, Orphazyme, Retrophin and Ultragenyx. Other financial or material support from Sanofi-Genzyme.

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Overview & Learning Objectives

In this activity, leading experts explore the latest advances in our understanding of the emerging spectrum of Pompe disease in the ERT era, including expanding phenotypes and the multisystem nature of disease, as well as the impact on patients and their caregivers.

This activity has been jointly provided by Oakstone and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians. read more

Target Audience

This activity has been designed to meet the educational needs of paediatricians, internal medicine physicians, cardiologists and neurologists involved in the multidisciplinary management of Pompe disease.


Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.


Prof. Damara Ortiz discloses: Grants/research support from Amicus, BioMarin, Sanofi-Genzyme and Takeda. Consultant/advisory boards for Amicus, Sanofi-Genzyme.

Prof. Virginia Kimonis discloses: Grants/research support from Sanofi-Genzyme. Consultant/advisory boards for Sanofi-Genzyme.

Prof. Loren Pena discloses: Grants/research support from Shire, Takeda. Consultant/advisory boards for Avexis, Orphazyme, Retrophin, Ultragenyx. Other financial or material support from Sanofi-Genzyme.

Content Reviewer

Walter Murray Yarbrough, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Alison Scott PhD has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA) European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: 29 September 2020. Date credits expire: 29 September 2021.

Learning Objectives

After watching this activity, participants should be better able to:

  • Discuss how successful ERT has led to the new phenotype of infantile-onset Pompe disease
  • Describe the multisystem disorders of late-onset Pompe disease
  • Explain the approaches that are being used to address the unmet treatment needs for Pompe disease

This content is intended for healthcare professionals only. Please confirm that you are a healthcare professional.

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Question 1/5
Which of the following emerging and experimental therapies for Pompe disease is designed to overcome treatment challenges associated with ERT reliant on exogenous GAA?

Emerging second-generation rhGAA-based ERTs (VAL-1221, AT-GAA and neo-GAA) have been engineered to improve targeted delivery and uptake of exogenous GAA.1,2

AAVB1-GAA is a targeted gene therapy (currently in preclinical development) designed to correct underlying GAA defects to overcome existing challenges and treatment burden associated with exogenous GAA ERT.1

AAV, adeno-associated virus; ERT, enzyme replacement therapy; GAA, acid alpha-glucosidase; rhGAA, recombinant human GAA.


  1. Do HV, et al. Ann Transl Med.2019;7:291.
  2. Pena LDM, et al. Neuromusc Dis. 2019;29:167–86.
Question 2/5
Which of the following statements is an accurate description of the current treatment landscape in Pompe disease?

ERT with alglucosidase alfa is FDA-indicated for patients with Pompe disease1 and is EMA-approved in adult and paediatric patients of all ages, with a confirmed diagnosis of Pompe disease (acid alpha-glucosidase deficiency).2

EMA, European Medicines Agency; ERT, enzyme replacement therapy; FDA, US Food and Drug Administration.


  1. FDA. Alglucosidase alfa (lumizyme) PI. 2020. Available at: (accessed September 2020).
  2. EMA. Alglucosidase alfa (myozyme) SmPC. 2020. Available at: (accessed September 2020).
Question 3/5
Newborn screening (NBS) test results from a dried blood spot show very low GAA activity in an infant patient. What laboratory tests are recommended to specifically aid a confirmatory diagnosis of Pompe disease?

Routine laboratory tests, including LFTs and RFTs, should be assessed when an inborn error of metabolism is suspected in a patient with metabolic stress,1 but would not specifically aid diagnosis of Pompe disease, in accordance with guideline recommendations for confirmatory tests following positive NBS test.2 Diagnostic testing for presumptive Pompe disease include GAA enzyme activity, targeted gene sequencing and evaluation of CK and HEX4 levels.3

CK, creatine kinase; CRP, C-reactive protein; GAA, acid alpha-glucosidase; HEX4, glucotetrasaccharide; LFTs, liver function tests; NBS, newborn screening; RFTs, renal function tests.


  1. Guerrero RB, et al. Ann Transl Med. 2018;6:470.
  2. Burton BK, et al. Pediatrics. 2017;140:e20160280.
  3. Klug TL, et al. Int J Neonatal Screen. 2020;6:11.
Question 4/5
Which further investigations would help differentially diagnose infantile- from late-onset Pompe disease, and what is the underlying rationale?

Cardiac involvement is prominent in patients with IOPD. Significant cardiac involvement is not usually observed in older children or adults with LOPD, and in the majority of LOPD cases, there is no cardiac involvement (although cardiac abnormalities may develop over time). The most prominent manifestation in LOPD is progressive muscle weakness.1 Initial clinical evaluation of infants with suspected Pompe disease can involve a chest X-ray to evaluate presence of cardiomegaly in its infantile form.2 VUS have been reported across the spectrum of Pompe disease (including classical-IOPD, non-classical IOPD and LOPD).3

ECG, electrocardiogram; echo, echocardiogram; HCM, hypertrophic cardiopmyopathy; IOPD, infantile-onset Pompe disease; LOPD, late-onset Pompe disease; VUS variants of unknown significance.


  1. Burton BK, et al. Pediatrics. 2017;140:e20160280.
  2. Tarnopolsky M, et al. Can J Neurol Sci. 2016;43:472–85.
  3. Klug TL, et al. Int J Neonatal Screen. 2020;6:11.
Question 5/5
Confirmatory tests for this patient reveal GAA enzyme activity <1%. Levels of HEX4 and CK are elevated. On clinical examination, the infant is affected by muscle weakness, but has not yet shown signs of feeding issues. Cardiac function tests reveal mild abnormalities, but cardiomegaly is absent on chest X-ray. What would be your next course of action and why?

GAA activity is <1% in all IOPD patients.1 Patients presenting with significant cardiomegaly at birth are defined as classical IOPD, whilst patients presenting without cardiomegaly are defined as atypical or non-classical IOPD.2 Significantly elevated levels of HEX4 and CK are reported in non-classical IOPD.3 ERT has shown greatest benefit if started prior to the onset of symptoms,3 supporting early intervention with ERT. Upon diagnosis and in conjunction with ERT induction, patients with IOPD should undergo respiratory assessment.4

CK, creatine kinase; ERT, enzyme replacement therapy; GAA, acid αlpha-glucosidase; HEX4, glucotetrasaccharide; IOPD, infantile-onset Pompe disease; LOPD, late-onset Pompe disease.


  1. Hahn A, Schänzer A. Ann Transl Med. 2019;7:283.
  2. Chien Y-H, et al. Mol Gen Metab Reports. 2020;23:100591.
  3. Klug TL, et al. Int J Neonatal Screen. 2020;6:11.
  4. Tarnopolsky M, et al. Can J Neurol Sci. 2016;43:472–85.
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