title: Morphological spectrum and clinical features of myopathies with tubular aggregates.
abstract: 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, immunohistochemical 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.
authors.affiliation: Institute of Neuropathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Funk
authors.forename: Chantal
authors.initials: C
authors.lastname: Ceuterick-de Groote
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Axel
authors.initials: A
authors.lastname: Meinhardt
authors.forename: Ana L
authors.initials: AL
authors.lastname: Taratuto
authors.forename: Jan
authors.initials: J
authors.lastname: De Bleecker
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.forename: Boel
authors.initials: B
authors.lastname: De Paepe
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schara
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.forename: Martin
authors.initials: M
authors.lastname: Häusler
authors.forename: Stefan
authors.initials: S
authors.lastname: Koppi
authors.forename: Matthias
authors.initials: M
authors.lastname: Maschke
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Lionel
authors.initials: L
authors.lastname: Van Maldergem
authors.forename: Stéphane
authors.initials: S
authors.lastname: Noel
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Zimmermann
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirth
authors.forename: Stefan
authors.initials: S
authors.lastname: Isenmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stadler
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001706:Biopsy / Q000379:methods; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000473:pathology*; D010375:Pedigree; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D055815:Young Adult