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 (
Glc(4) ), 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.
Glc(4) 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
Glc(4) had 94% sensitivity and 84% specificity for
Pompe disease. We propose
Glc(4) 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.