title: Exertional rhabdomyolysis and exercise intolerance revealing dystrophinopathies.
abstract: Exercise intolerance associated with myalgias, muscle cramps or myoglobinuria may be associated with a dystrophinopathy. A search for abnormal dystrophin expression (using immunohistochemistry, immunoblot and DNA analysis) was carried out in a series of 15 patients. They were selected because they presented exercise intolerance, negative biochemical tests (lipid, glycogen and mitochondrial metabolism) and abnormal immunohistochemistry with at least one anti-dystrophin antibody (anti-Dys 1, rod domain; anti-Dys 2, C terminus; anti-Dys 3, N terminus). Lack of anti-Dys 1 immunoreactivity was seen in three patients and abnormal immunoreactivity with all three anti-dystrophin antibodies in two. Immunoblot confirmed the dystrophinopathy in these five patients only, and multiplex polymerase chain reaction DNA analysis revealed a deletion in the dystrophin gene in two of these patients, affecting the proximal 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 reported in the literature, are described and reveal that exercise intolerance associated with dystrophinopathy displays characteristic clinical, biological and immunohistochemical features and defines a new dystrophinopathy phenotype. The absence of staining in the rod domain provides a secure diagnosis of this syndrome. Dystrophinopathy is one etiology of idiopathic myoglobinuria, requiring genetic counseling.
authors.affiliation: Department of Pathology and Neuropathology, Hôpital de la Timone, Marseille, France.
authors.forename: D
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: A M
authors.initials: AM
authors.lastname: Baeta Machado
authors.forename: G A
authors.initials: GA
authors.lastname: Putzu
authors.forename: P
authors.initials: P
authors.lastname: Malzac
authors.forename: M A
authors.initials: MA
authors.lastname: Voelckel
authors.forename: J F
authors.initials: JF
authors.lastname: Pellissier
mesh_terms: D000293:Adolescent; D000328:Adult; D016189:Dystrophin / Q000737:chemistry* / Q000276:immunology; D015444:Exercise; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009120:Muscle Cramp / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism / Q000503:physiopathology; D009212:Myoglobinuria / Q000378:metabolism / Q000503:physiopathology; D012206:Rhabdomyolysis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D016189:Dystrophin