EXERTIONAL RHABDOMYOLYSIS AND EXERCISE INTOLERANCE REVEALING DYSTROPHINOPATHIES

Exercise intolerance associated with myalgias, muscle cramps or myoglo binuria may be associated with a dystrophinopathy. A search for abnorm al dystrophin expression (using immunohistochemistry, immunoblot and D NA analysis) was carried out in a series of 15 patients. They were sel ected because they presented exercise intolerance, negative biochemica l tests (lipid, glycogen and mitochondrial metabolism) and abnormal im munohistochemistry with at least one anti-dystrophin antibody (anti-Dy s I, rod domain; anti-Dys 2, C terminus; anti-Dys 3, N terminus). Lack of anti-Dys 1 immunoreactivity was seen in three patients and abnorma l immunoreactivity with all three anti-dystrophin antibodies in two. I mmunoblot confirmed the dystrophinopathy in these five patients only, and multiplex polymerase chain reaction DNA analysis revealed a deleti on in the dystrophin gene in two of these patients, affecting the prox imal part of the rod domain in one and the distal part of this domain in the other. The clinical, biological and histopathological features of the five patients reported here, together with the previous cases r eported in the literature, are described and reveal that exercise into lerance associated with dystrophinopathy displays characteristic clini cal, biological and immunohistochemical features and defines a new dys trophinopathy phenotype. The absence of staining in the rod domain pro vides a secure diagnosis of this syndrome. Dystrophinopathy is one eti ology of idiopathic myoglobinuria, requiring genetic counseling.