Caveolin Inclusion Myopathy

We previously reported a new, autosomal dominant or sporadic, proximal myopathy characterized by mild myalgias and muscle weakness, and the presence of intracytoplasmic, hexagonally cross‐linked tubular arrays in type 2 muscle fibres ( Ann Neurol 45:512, 1999). We report the ultrastructural and immunohistochemical characterization of identical inclusions in another patient with an apparent sporadic form of the disease. This 45‐year old male underwent quadriceps femoris muscle biopsy for an upper extremity myalgias and CK activity found at 1,900 (N < 220 iU/L). He had no family history of muscle disease and parents were not consanguineous. Gomori stain revealed rod‐shaped intensely blue cytoplasmic inclusions in type 2 muscle fibres reminiscent of nemaline bodies. Inclusions were strongly positive for caveolin‐3 and negative for desmin, actin, myosin, vimentin, ubiquitin and components of sarcolemma. They displayed characteristic hexagonal crystalloid tubular arrays joined by double bridging arms and were not connected to cytoskeleton or any other organelles. The inclusions were very often surrounded by globular small structures measuring approximately 37 nm and reminiscent of caveolae. This is the first demonstration of chemical nature of the cytoplasmic inclusions in this condition. This disease is probably more common than reported, since the inclusions are very similar to nemaline bodies with light and electron microscopy, and misdiagnosed without grid tilting. At this point, it is not clear whether the underlying process is an excessive formation of caveolae or inability of cell to discharge or degrade caveolin, which conglomerate in the large intracytoplasmic masses.