Samuela A Fernandes1, Aleena A Khan1, Tracy Boggs2, Michael Bowling3, Stephanie Austin1, Mihaela Stefanescu1, Laura Case4, Priya S Kishnani1. 1. Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine Durham North Carolina USA. 2. Division of Physical Therapy, Department of Community and Family Medicine Duke University School of Medicine Durham North Carolina USA. 3. Multi-Dimensional Image Processing Laboratory, Department of Radiology Duke University School of Medicine Durham North Carolina USA. 4. Doctor of Physical Therapy Division, Department of Orthopedics Duke University School of Medicine Durham North Carolina USA.
Abstract
OBJECTIVE: Since the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement. METHODS: Eleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7-17 years, received whole-body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4. RESULTS: Patients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = -.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD. CONCLUSION: In the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.
OBJECTIVE: Since the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement. METHODS: Eleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7-17 years, received whole-body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4. RESULTS: Patients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = -.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD. CONCLUSION: In the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.
Authors: Federica Montagnese; E Barca; O Musumeci; S Mondello; A Migliorato; A Ciranni; C Rodolico; P De Filippi; C Danesino; A Toscano Journal: J Neurol Date: 2015-02-12 Impact factor: 4.849
Authors: Ans T van der Ploeg; Richard Barohn; Lisa Carlson; Joel Charrow; Paula R Clemens; Robert J Hopkin; Priya S Kishnani; Pascal Laforêt; Claire Morgan; Sharon Nations; Alan Pestronk; Horacio Plotkin; Barry E Rosenbloom; Katherine B Sims; Elisa Tsao Journal: Mol Genet Metab Date: 2012-09-17 Impact factor: 4.797
Authors: Sarah P Young; Haoyue Zhang; Deyanira Corzo; Beth L Thurberg; Deeksha Bali; Priya S Kishnani; David S Millington Journal: Genet Med Date: 2009-07 Impact factor: 8.822