Résumé :
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Reducing body myopathy (RBM), described by Brooke and Neville in 1972, is a rare congenital disorder defined by the presence of cytoplasmic inclusions that reduce nitro-blue tetrazolium (NBT) and thus stain strongly with the menadione-NBT stain. RBM is caused by mutations in FHL1 gene, on chromosome Xq27.2.Aim: to report clinical, morphological and ultrastructural features in a new family suffering from RBM, emphasizing unusual clinical and morphological features.Patients/Methods: Clinical examination, CK level, EMG, respiratory function and cardiological test were performed in a boy and his mother. A muscle biopsy performed on both patients was processed for histochemical and ultrastructural analysis. Molecular analysis was accomplished by sequencing coding regions of FHL1 gene. Results: The proband presented at the age of 2 years with hypotonia, waddling gait, and difficulties rising up his arms. Examination revealed prominent proximal weakness and slightly asymmetrical atrophy of four limbs, trunk and neck muscles and scapular winging. CK levels were x10 and EMG showed myopathic features. Examination of the mother showed a strikingly asymmetric weakness and atrophy involving the left side of the body. The clinical course of the child rapidly progressed; he developed rigidity of the spine and neck, severe respiratory insufficiency and lost ambulation at the age of 4 years. No signs of cardiomyopathy were recorded. Muscle biopsies showed severe myopathic abnormalities with marked variation of fiber size, increased numbers of internal nuclei, fibro fatty tissue proliferation, and type I fiber predominance. In both cases several fibers contained large inclusion bodies strongly reacting with menadione-NBT. Under electron microscopy reducing bodies and cytoplasmic bodies were observed in the mother and his child. Less affected fibers showed coarse, dense granular material in the subsarcolemma and between the myofibrils. In more advanced lesions this material coalesced to form reducing bodies often associated to cytoplasmic bodies. Autophagic vacuoles were additional findings. Molecular analysis revealed a neo mutation p.C132F in 2nd LIM domain of FHL1 in the mother and his child.Discussion: We have identified a new family suffering from reducing body myopathy characterized by severe, early-onset and rapidly progressive asymmetrical weakness. Detailed electron microscopic analysis performed in our patients allowed us to propose sequential events leading to reducing body formation.
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