Myopathy with hexagonally cross-linked crystalloid inclusions: delineation of a clinico-pathological entity
Claeys, Kristl × Pellissier, Jean-François Garcia-Bragado, Federico Weis, Joachim Urtizberea, Andoni Poza, Juan-Jose Cobo, Ana-Maria Stoltenburg, Gisela Figarella-Branger, Dominique Willems, Patrick J Depuydt, Christophe E Kleiner, Wolfgang Pouget, Jean Piraud, Monique Brochier, Guy Romero, Norma B Fardeau, Michel Goebel, Hans H Bönnemann, Carsten G Voit, Thomas Eymard, Bruno Laforêt, Pascal #
A novel myopathy characterized by hexagonally cross-linked tubular arrays has been reported in five patients. We studied the clinical and histopathological features of five additional unrelated patients with this myopathy. Patients experienced exercise intolerance with exercise-induced myalgia and weakness, without rhabdomyolysis. One patient additionally presented mild permanent pelvic girdle muscle weakness. Age at onset varied between 13 and 56 years. The inclusions were eosinophilic on H and E, bright red with modified Gomori's trichrome stains, present in type 2 fibers, and revealed immunoreactivity selectively for a caveolin-3-antibody. Ultrastructurally, the inclusions showed a highly organized, hexagonally cross-linked crystalloid structure. Mutations in the caveolin-3 encoding gene were excluded. Biochemical assessment of glycogenolysis in muscle was normal. Inherited or sporadic myopathy with hexagonally cross-linked tubular arrays is associated with a homogeneous clinical and histopathological phenotype. This myopathy should be included in the differential diagnosis of patients with exercise intolerance and myalgia.