TY  - JOUR
A1  - Kulessa, Martin
A1  - Weyer‐Menkhoff, Iris
A1  - Viergutz, Lara
A1  - Kornblum, Cornelia
A1  - Claeys, Kristl G.
A1  - Schneider, Ilka
A1  - Plöckinger, Ursula
A1  - Young, Peter
A1  - Boentert, Matthias
A1  - Vielhaber, Stefan
A1  - Mawrin, Christian
A1  - Bergmann, Markus
A1  - Weis, Joachim
A1  - Ziagaki, Athanasia
A1  - Stenzel, Werner
A1  - Deschauer, Marcus
A1  - Nolte, Dagmar
A1  - Hahn, Andreas
A1  - Schoser, Benedikt
A1  - Schänzer, Anne
T1  - An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease
T2  - Neuropathology & applied neurobiology
N2  - Aims: Pompe disease is caused by pathogenic mutations in the alpha 1,4‐glucosidase (GAA) gene and in patients with late onset Pome disease (LOPD), genotype–phenotype correlations are unpredictable. Skeletal muscle pathology includes glycogen accumulation and altered autophagy of various degrees. A correlation of the muscle morphology with clinical features and the genetic background in GAA may contribute to the understanding of the phenotypic variability.
Methods: Muscle biopsies taken before enzyme replacement therapy were analysed from 53 patients with LOPD. On resin sections, glycogen accumulation, fibrosis, autophagic vacuoles and the degree of muscle damage (morphology‐score) were analysed and the results were compared with clinical findings. Additional autophagy markers microtubule‐associated protein 1A/1B‐light chain 3, p62 and Bcl2‐associated athanogene 3 were analysed on cryosections from 22 LOPD biopsies.
Results: The myopathology showed a high variability with, in most patients, a moderate glycogen accumulation and a low morphology‐score. High morphology‐scores were associated with increased fibrosis and autophagy highlighting the role of autophagy in severe stages of skeletal muscle damage. The morphology‐score did not correlate with the patient's age at biopsy, disease duration, nor with the residual GAA enzyme activity or creatine‐kinase levels. In 37 patients with LOPD, genetic analysis identified the most frequent mutation, c.‐32‐13T>G, in 95%, most commonly in combination with c.525delT (19%). No significant correlation was found between the different GAA genotypes and muscle morphology type.
Conclusions: Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57030
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-570305
SN  - 1365-2990
SN  - 0305-184
VL  - 46.2020
SP  - 359–374
EP  - 359–374
PB  - Wiley-Blackwell
CY  - Oxford [u.a.]
ER  -