An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease.
GAA
GSD II
autophagy
genotype
late onset Pompe disease (LOPD)
lysosomal storage disease
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
21
06
2019
accepted:
07
08
2019
pubmed:
24
9
2019
medline:
5
6
2021
entrez:
24
9
2019
Statut:
ppublish
Résumé
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. 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. 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. Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
359-374Informations de copyright
© 2019 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
Références
Hoefsloot LH, Hoogeveen-Westerveld M, Reuser AJ, Oostra BA. Characterization of the human lysosomal alpha-glucosidase gene. Biochem J 1990; 272: 493-7
Kroos M, Hoogeveen-Westerveld M, Michelakakis H, Pomponio R, Van der Ploeg A, Halley D, et al. Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants. Hum Mut 2012; 33: 1161-5
Kroos M, Hoogeveen-Westerveld M, van der Ploeg A, Reuser AJ. The genotype-phenotype correlation in Pompe disease. Am J Med Genet C Semin Med Genet 2012; 160: 59-68
Kroos MA, Pomponio RJ, Hagemans ML, Keulemans JL, Phipps M, DeRiso M, et al. Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype. Neurology 2007; 68: 110-5
De Filippi P, Saeidi K, Ravaglia S, Dardis A, Angelini C, Mongini T, et al. Genotype-phenotype correlation in Pompe disease, a step forward. Orphanet J Rare Dis 2014; 9: 102
Montagnese F, Barca E, Musumeci O, Mondello S, Migliorato A, Ciranni A, et al. Clinical and molecular aspects of 30 patients with late-onset Pompe disease (LOPD): unusual features and response to treatment. J Neurol 2015; 262: 968-78
Wens SC, van Gelder CM, Kruijshaar ME, de Vries JM, van der Beek NA, Reuser AJ, et al. Phenotypical variation within 22 families with Pompe disease. Orphanet J Rare Dis 2013; 8: 182
Sampaolo S, Esposito T, Farina O, Formicola D, Diodato D, Gianfrancesco F, et al. Distinct disease phenotypes linked to different combinations of GAA mutations in a large late-onset GSDII sibship. Orphanet J Rare Dis 2013; 8: 159
Löscher WN, Huemer M, Stulnig TM, Simschitz P, Iglseder S, Eggers C, et al. Pompe disease in Austria: clinical, genetic and epidemiological aspects. J Neurol 2018; 265: 159-64
Hahn A, Praetorius S, Karabul N, Diessel J, Schmidt D, Motz R, et al. Outcome of patients with classical infantile pompe disease receiving enzyme replacement therapy in Germany. JIMD Rep 2015; 20: 65-75
Montalvo AL, Bembi B, Donnarumma M, Filocamo M, Parenti G, Rossi M, et al. Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II. Hum Mut 2006; 27: 999-1006
Hirschhorn R, Reuser AJJ. Glykogen storage disease type II: acid alpha-glucosidase (acid maltase) defiency. In The Metabolic and Molecular Bases of Inherited Disease. Chapter 135. Eds D Valle, O Simell. New York: McGraw-Hill, 2001; 3389-420
Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8: 267-88
van den Hout HM, Hop W, van Diggelen OP, Smeitink JA, Smit GP, Poll-The BT, et al. The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature. Pediatrics 2003; 112: 332-40
Winkel LP, Hagemans ML, van Doorn PA, Loonen MC, Hop WJ, Reuser AJ, et al. The natural course of non-classic Pompe's disease; a review of 225 published cases. J Neurol 2005; 252: 875-84
Herzog A, Hartung R, Reuser AJ, Hermanns P, Runz H, Karabul N, et al. A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations. Orphanet J Rare 2012; 7: 35
Schoser BG, Müller-Höcker J, Horvath R, Gempel K, Pongratz D, Lochmüller H, et al. Adult-onset glycogen storage disease type 2: clinico-pathological phenotype revisited. Neuropathol Appl Neurobiol 2007; 33: 544-59
Joshi PR, Glaser D, Schmidt S, Vorgerd M, Winterholler M, Eger K, et al. Molecular diagnosis of German patients with late-onset glycogen storage disease type II. J Inherit Metabol Dis 2008; 31 (Suppl. 2): S261-5
Gungor D, de Vries JM, Hop WC, Reuser AJ, van Doorn PA, van der Ploeg AT, et al. Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy. Orphanet J Rare 2011; 6: 34
Toscano A, Schoser B. Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review. J Neurol 2013; 260: 951-9
Schänzer A, Kaiser AK, Mühlfeld C, Kulessa M, Paulus W, von Pein H, et al. Quantification of muscle pathology in infantile Pompe disease. Neuromusc Dis 2017; 27: 141-52
van der Ploeg A, Carlier PG, Carlier RY, Kissel JT, Schoser B, Wenninger S, et al. Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: the EMBASSY Study. Mol Genet Metabol 2016; 119: 115-23
Müller-Felber W, Horvath R, Gempel K, Podskarbi T, Shin Y, Pongratz D, et al. Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients. Neuromusc Dis 2007; 17: 698-706
Malicdan MC, Nishino I. Autophagy in lysosomal myopathies. Brain Pathol 2012; 22: 82-8
Nascimbeni AC, Fanin M, Tasca E, Angelini C, Sandri M. Impaired autophagy affects acid alpha-glucosidase processing and enzyme replacement therapy efficacy in late-onset glycogen storage disease type II. Neuropathol Appl Neurobiol 2015; 41: 672-5
Raben N, Wong A, Ralston E, Myerowitz R. Autophagy and mitochondria in Pompe disease: nothing is so new as what has long been forgotten. Am J Med Genet 2012; 160: 13-21
Chien YH, Lee NC, Huang PH, Lee WT, Thurberg BL, Hwu WL. Early pathologic changes and responses to treatment in patients with later-onset Pompe disease. Pediatr Neurol 2012; 46: 168-71
Feeney EJ, Austin S, Chien YH, Mandel H, Schoser B, Prater S, et al. The value of muscle biopsies in Pompe disease: identifying lipofuscin inclusions in juvenile- and adult-onset patients. Acta Neuropathol Comm 2014; 2: 2
Ripolone M, Violano R, Ronchi D, Mondello S, Nascimbeni A, Colombo I, et al. Effects of short-to-long term enzyme replacement therapy (ERT) on skeletal muscle tissue in late onset Pompe disease (LOPD). Neuropathol Appl Neurobiol 2018; 44: 449-62
Thurberg BL, Lynch Maloney C, Vaccaro C, Afonso K, Tsai AC, Bossen E, et al. Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease. Lab Invest 2006; 86: 1208-20
Dubowitz V, Sewry C, Oldfords A. Muscle Biopsy: A Practical Approach. London: Saunders Elsevier, 2013
Schänzer A, Giese K, Viergutz L, Hahn A. Letter to the editors: concerning ‘divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state’ by Takashi et al. and Letter to the Editors by Ortolano et al. Mol Genet Metabol Rep 2017; 12: 33-4
Schänzer A, Görlach J, Claudi K, Hahn A. Severe distal muscle involvement and mild sensory neuropathy in a boy with infantile onset Pompe disease treated with enzyme replacement therapy for 6 years. Neuromusc Disord 2019; 29: 477-82
Golsari A, Nasimzadah A, Thomalla G, Keller S, Gerloff C, Magnus T. Prevalence of adult Pompe disease in patients with proximal myopathic syndrome and undiagnosed muscle biopsy. Neuromusc Dis 2018; 28: 257-61
Reuser AJ, Van Den Hout H, Bijvoet AG, Kroos MA, Verbeet MP, Van Der Ploeg AT. Enzyme therapy for Pompe disease: from science to industrial enterprise. Eur J Pediatr 2002; 161 (Suppl. 1): S106-11
Neel BA, Lin Y, Pessin JE. Skeletal muscle autophagy: a new metabolic regulator. Trends Endocrinol Metabol 2013; 24: 635-43
Raben N, Hill V, Shea L, Takikita S, Baum R, Mizushima N, et al. Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. Hum Mol Genet 2008; 17: 3897-908
Nascimbeni AC, Fanin M, Masiero E, Angelini C, Sandri M. Impaired autophagy contributes to muscle atrophy in glycogen storage disease type II patients. Autophagy 2012; 8: 1697-700
Lim JA, Li L, Raben N. Pompe disease: from pathophysiology to therapy and back again. Front Aging Neurosci 2014; 6: 177
Lim JA, Sun B, Puertollano R, Raben N. Therapeutic benefit of autophagy modulation in Pompe disease. Mol Ther 2018; 26: 1783-96
Lim JA, Li L, Shirihai OS, Trudeau KM, Puertollano R, Raben N. Modulation of mTOR signaling as a strategy for the treatment of Pompe disease. EMBO Mol Med 2017; 9: 353-70
Raben N, Schreiner C, Baum R, Takikita S, Xu S, Xie T, et al. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder-murine Pompe disease. Autophagy 2010; 6: 1078-89
Lim J, Meena N, Raben N. Pros and cons of different ways to address dysfunctional autophagy in Pompe disease. Ann Trans Med 2019; 7: 279
Ulbricht A, Gehlert S, Leciejewski B, Schiffer T, Bloch W, Höhfeld J. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy 2015; 11: 538-46
Klimek C, Kathage B, Wordehoff J, Höhfeld J. BAG3-mediated proteostasis at a glance. J Cell Sci 2017; 130: 2781-8
Xu S, Galperin M, Melvin G, Horowits R, Raben N, Plotz P, et al. Impaired organization and function of myofilaments in single muscle fibers from a mouse model of Pompe disease. J Appl Physiol 2010; 108: 1383-8
Chien YH, Lee NC, Thurberg BL, Chiang SC, Zhang XK, Keutzer J, et al. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics 2009; 124: e1116-25
Chien YH, Lee NC, Huang HJ, Thurberg BL, Tsai FJ, Hwu WL. Later-onset Pompe disease: early detection and early treatment initiation enabled by newborn screening. J Pediatr 2011; 158: 1023-7.e1
Huie ML, Chen AS, Tsujino S, Shanske S, DiMauro S, Engel AG, et al. Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T->G) mutation in a majority of patients and a novel IVS10 (+1GT->CT) mutation. Hum Mol Genet 1994; 3: 2231-6
Johnson K, Topf A, Bertoli M, Phillips L, Claeys KG, Stojanovic VR, et al. Identification of GAA variants through whole exome sequencing targeted to a cohort of 606 patients with unexplained limb-girdle muscle weakness. Orphanet J Rare 2017; 12: 173
R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2018. Available at https://www.R-project.org/