Morphological spectrum and clinical features of myopathies with tubular aggregates
Fabian Funk1,2,3, Chantal Ceuterick-de Groote4, Jean-Jacques Martin4,5, Axel Meinhardt1, Ana L. Taratuto6, Jan De Bleecker7, Rudy Van Coster8, Boel De Paepe8, Ulrike Schara9, Matthias Vorgerd10, Martin Häusler11, Stefan Koppi12, Matthias Maschke13, Peter De Jonghe5, Lionel Van Maldergem14, Stéphane Noel15, Christoph W. Zimmermann16, Stefan Wirth17, Stefan Isenmann18, Rudolf Stadler19, J. Michael Schröder1,3, Jörg B. Schulz2,3, Joachim Weis1,3 and Kristl G. Claeys1,2,3
1Institute of Neuropathology, RWTH Aachen University, Aachen, Germany, 2Department of Neurology, RWTH Aachen University, Aachen, Germany, 3JARA Translational Brain Medicine, 4Laboratory of Ultrastructural Neuropathology, Institute Born-Bunge, University of Antwerpen, Antwerpen, Belgium, 5Department of Neurology, University Hospital Antwerpen, Antwerpen, Belgium, 6Institute for Neurological Research, FLENI, Buenos Aires, Argentina, 7Department of Neurology, University Hospital Gent, Gent, Belgium, 8Department of Pediatrics, Division of Pediatric Neurology and Metabolism, University Hospital Gent, Gent, Belgium, 9Department of Pediatric Neurology, University of Essen, Essen, Germany, 10Department of Neurology, University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany, 11Department of Neuropediatrics, RWTH Aachen University, Aachen, Germany, 12Department of Neurology, Regional Hospital of Rankweil 1, Rankweil, Austria, 13Department of Neurology and Neurophysiology, Hospital Barmherzige Brüder, Trier, Germany, 14Centre de Génétique Mumaine, Université de Franche-Comté, Besançon, France, 15Department of Neurology, University Hospital, Charleroi, Belgium, 16Department of Neurology, St. Josef Hospital/Academic Teaching Hospital of the University of Essen, Oberhausen, Germany, 17Children's Hospital, Helios Klinikum Wuppertal, Wuppertal, Germany, 18Department of Neurology, Helios Klinikum Wuppertal, Wuppertal and University of Witten/Herdecke, Germany and 19Department of Dermatology, Johannes-Wesling-Klinik, Minden, Germany.
Offprint requests to: PD Dr. med. Kristl Claeys, Department of Neurology and Institute of Neuropathology, University Hospital RWTH, Pauwelsstr. 30, 52074 Aachen, Germany. e-mail: kclaeys@ukaachen.de
Summary. Tubular aggregates (TAs) are aggregates of densely packed tubules in human skeletal muscle fibers with particular histochemical and ultrastructural features that most probably arise from the sarcoplasmic reticulum. Some studies have shown an additional mitochondrial origin of TAs. We studied the histopathological spectrum and clinical features in a large cohort of patients with TAs in their muscle biopsy (106 biopsies), derived from our muscle biopsy archive (15,412 biopsies in total). In particular, we examined light microscopic, enzyme histochemical, immunohisto-chemical and ultrastructural features in the muscle biopsies, as well as the patients’ clinical data. We found TAs in 0.5% of all muscle biopsies. Based on the size of TAs, we identified two sub-groups: (1) myopathies with large TAs (29 biopsies) in type 2 fibers and sometimes also in type 1 fibers, absence of any other associated disorder, and a familial history in half of the cases, and (2) myopathies with small TAs (77 biopsies), exclusively in type 2 fibers, presence of another associated disease in the majority of patients and mostly no familial history. In the sub-group with large TAs, we observed a high variability of ultrastructural changes. The most frequent clinical symptom in both groups was limb muscle weakness. No significant differences in clinical presentation, age at onset or disease duration at the time of biopsy were found between the two groups. In conclusion, myopathies with TAs can be sub-divided into a group with large TAs, probably corresponding to the so-called primary TA myopathies, and into a group with small TAs as a feature of another underlying condition. Histol Histopathol 28, 1041-1054 (2013)
Key words: Tubular aggregate myopathy, TAM, Skeletal muscle, Ultrastructure, Sarcoplasmic reticulum
DOI: 10.14670/HH-28.1041