title: Quantification of muscle pathology in infantile Pompe disease.
abstract: The effects of enzyme replacement therapy (ERT) in infantile Pompe disease are variable, necessitating the identification of biomarkers to assess the severity of disease and response to ERT. The aims of this study were to investigate whether quantification of muscle pathology in infantile Pompe disease prior to and during ERT is feasible at the light microscope, and to develop a score that summarizes the degree of muscle pathology in a comprehensive manner from PAS-stained resin sections alone. We, therefore, determined glycogen load, extent of muscle fibre disruption, and amount of autophagic vacuoles in resin-embedded muscle biopsy specimens from 11 infantile Pompe patients and 2 with early childhood phenotype by quantitative methods, correlated the findings with ultrastructural analyses, compared PAS-stained resin sections with conventional PAS-stained cryosections, and related the quantified degree of muscle damage from infantile patients to the effects of ERT. Comparison of electron and light microscopic findings demonstrated that important alterations of skeletal muscle morphology can also be depicted by examining PAS stained resin sections. Infantile patients with good response to ERT had lower muscle pathology score values prior to and during ERT than those with moderate and poor response, but the number of tissue samples available for evaluation was limited. These findings suggest that quantification of muscle pathology by analysing PAS stained resin sections is in principle feasible and useful to monitor disease progression and therapy response. These results have to be validated by investigating a larger group of patients.
authors.affiliation: Institute of Neuropathology, Justus Liebig University, Gießen, Germany. Electronic address: anne.schaenzer@patho.med.uni-giessen.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Schänzer
authors.affiliation: Institute of Neuropathology, Justus Liebig University, Gießen, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Kaiser
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.affiliation: Institute of Neuropathology, Justus Liebig University, Gießen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kulessa
authors.affiliation: Institute of Neuropathology, University Medical Center, Münster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Department of Neuropathology, University Medical Center of JGU-University, Mainz, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: von Pein
authors.affiliation: Division of Metabolism, Children's Research Center, University Children's Hospital, Zürich, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Rohrbach
authors.affiliation: Institute of Neuropathology, Justus Liebig University, Gießen, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Viergutz
authors.affiliation: Villa Metabolica, University Medical Center of JGU-University, Mainz, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Mengel
authors.affiliation: Department of Pediatrics, Westfälische Wilhelms University, Münster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Marquardt
authors.affiliation: Department of Child Neurology, Justus Liebig University, Gießen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neubauer
authors.affiliation: Institute of Neuropathology, Justus Liebig University, Gießen, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Acker
authors.affiliation: Department of Child Neurology, Justus Liebig University, Gießen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology* / Q000648:ultrastructure; D012720:Severity of Illness Index; D000520:alpha-Glucosidases / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: Acid maltase deficiency; Autophagy; Enzyme replacement therapy; Glycogen storage disease type II; Lysosomal storage disease; Pompe disease