Get access

Assessing disease severity in Pompe disease: The roles of a urinary glucose tetrasaccharide biomarker and imaging techniques

Authors

  • Sarah P. Young,

    Corresponding author
    • DUHS Biochemical Genetics Lab, 801-6 Capitola Drive, Durham, NC 27713.
    Search for more papers by this author
    • Sarah P. Young (Pediatrics Medical Genetics, Duke University Medical Center, North Carolina) is the assistant director of the Duke Biochemical Genetics Laboratory. The main focus of her research is the development and application of biomarker assays for inherited metabolic diseases, including Pompe disease and other lysosomal storage disorders.

  • Monique Piraud,

    Search for more papers by this author
    • Monique Piraud (Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Bron) is a biologist who has been involved in the diagnosis of metabolic disorders, particularly lysosomal storage disorders and glycogenoses, for more than 25 years.

  • Jennifer L. Goldstein,

    Search for more papers by this author
    • Jennifer L. Goldstein (Pediatrics Medical Genetics, Duke University Medical Center, North Carolina) is a clinical research coordinator with a strong interest in laboratory diagnosis of glycogen storage diseases. Other interests are creatine deficiency syndromes, molybdenum cofactor disorders, newborn screening, and autism research.

  • Haoyue Zhang,

    Search for more papers by this author
    • Haoyue Zhang (Pediatrics Medical Genetics, Duke University Medical Center, North Carolina) is a senior research scientist in the Biochemical Genetics Laboratory at Duke University. She has worked on the quantification of the glucose tetrasaccharide in urine and other biomarkers for lysosomal storage disease for 7 years.

  • Catherine Rehder,

    Search for more papers by this author
    • Catherine Rehder (Pathology, Duke University Medical Center, North Carolina) is director of the Molecular Diagnostics and Cytogenetics Laboratories at Duke. She has been involved with genotyping patients with Pompe disease and other metabolic diseases for the past 5 years through gene sequencing.

  • Pascal Laforet,

    Search for more papers by this author
    • Pascal Laforet (Institut de Myologie, Hospital Pitié-Salpêtrière, Paris) is a medical doctor who is dedicated to the care and clinical research in neuromuscular disorders. He has been involved in clinical trials for the treatment of muscular disorders and especially in metabolic diseases.

  • Priya S. Kishnani,

    Search for more papers by this author
    • Priya S. Kishnani (Pediatrics Medical Genetics, Duke University Medical Center, North Carolina) is Chief of Medical Genetics, Professor of Pediatrics, and a clinician scientist at Duke who is dedicated to the care and treatment of individuals with Pompe disease and other metabolic disorders. She has been involved in numerous clinical trials for the treatment of Pompe disease, Down syndrome, and many other conditions. She continues to research new therapies for Pompe disease, Down syndrome, and other glycogen storage diseases.

  • David S. Millington,

    Search for more papers by this author
    • David S. Millington (Pediatrics Medical Genetics, Duke University Medical Center, North Carolina) is a research scientist and director of the Biochemical Genetics Laboratory. He is primarily interested in the development of diagnostic and newborn screening tests for rare genetic disorders.

  • Mustafa R. Bashir,

    Search for more papers by this author
    • Mustafa R. Bashir (Department of Radiology, Duke University Medical Center, North Carolina) is an abdominal Radiologist with a strong interest in magnetic resonance imaging. He has active research interests in liver and whole-body MRI, particularly in metabolic imaging, for both diagnosis and treatment monitoring.

  • Deeksha S. Bali

    Search for more papers by this author
    • Deeksha S. Bali (Pediatrics Medical Genetics, Duke University Medical Center, North Carolina) is director of the Duke Glycogen Storage Disease laboratory and has been highly involved in laboratory diagnosis and research on Pompe disease and other glycogen storage diseases for the past 15 years. New methods for non-invasive diagnosis of lysosomal storage diseases have been developed so that patients can benefit from early diagnosis and initiation of treatment.


  • How to cite this article: Young SP, Piraud M, Goldstein JL, Zhang H, Rehder C, Laforet P, Kishnani PS, Millington DS, Bashir M, Bali D. 2012. Assessing disease severity in Pompe disease: The roles of a urinary glucose tetrasaccharide biomarker and imaging techniques. Am J Med Genet Part C Semin Med Genet 160C:50–58.

Abstract

Defining disease severity in patients with Pompe disease is important for prognosis and monitoring the response to therapies. Current approaches include qualitative and quantitative assessments of the disease burden, and clinical measures of the impact of the disease on affected systems. The aims of this manuscript were to review a noninvasive urinary glucose tetrasaccharide biomarker of glycogen storage, and to discuss advances in imaging techniques for determining the disease burden in Pompe disease. The glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc4), is a glycogen-derived limit dextrin that correlates with the extent of glycogen accumulation in skeletal muscle. As such, it is more useful than traditional biomarkers of tissue damage, such as CK and AST, for monitoring the response to enzyme replacement therapy in patients with Pompe disease. Glc4 is also useful as an adjunctive diagnostic test for Pompe disease when performed in conjunction with acid alpha-glucosidase activity measurements. Review of clinical records of 208 patients evaluated for Pompe disease by this approach showed Glc4 had 94% sensitivity and 84% specificity for Pompe disease. We propose Glc4 is useful as an overall measure of disease burden, but does not provide information on the location and distribution of excess glycogen accumulation. In this manuscript we also review magnetic resonance spectroscopy and imaging techniques as alternative, noninvasive tools for quantifying glycogen and detailing changes, such as fibrofatty muscle degeneration, in specific muscle groups in Pompe disease. These techniques show promise as a means of monitoring disease progression and the response to treatment in Pompe disease. © 2012 Wiley Periodicals, Inc.

Get access to the full text of this article

Ancillary