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Reducing body myopathy
Reducing body myopathy (RBM) is a rare muscle disorder marked by progressive muscle weakness and the presence of characteristic inclusion bodies in affected muscle fibres.
ORPHA:97239Classification level: Disorder
The prevalence is unknown: although some sporadic cases have been described, only four families with RBM have been reported in the literature so far.
The age of onset, speed of progression and severity of the disease vary significantly between patients, even between affected members of the same family. Although early development is generally normal (up to 2 years of age), onset during infancy or early childhood appears to be associated with severe myopathy, hypotonia and rapidly progressive muscle weakness leading to death due to respiratory insufficiency within the first five years of life. Onset during childhood or adulthood is characterised by mainly proximal muscle weakness, a rigid spine syndrome and a slowly progressive disease course.
Both sporadic and familial cases of RBM are caused by mutations in the gene encoding the four-and-a-half LIM domain 1 protein (FHL1; Xq27.2).
As the clinical picture is highly variable (EMG reveals mixed myogenic patterns), diagnosis relies on recognition of the typical histopathological findings at muscle biopsy: the non-membrane-bound inclusions reduce nitro-blue tetrazolium (hence the name `reducing body myopathy') and are located in the cytoplasm, usually close to the degenerating nucleus. Electron microscopy reveals that the inclusions consist of a fine granular material and immunohistochemical analysis reveals the presence of aggresome-like proteins.
The differential diagnosis should include other disorders with reducing bodies (e.g. acid maltase deficiency) and other congenital myopathies in familial cases (see these terms). Sarcotubular myopathy may also be considered in patients with less severe forms of the disease.
The mode of transmission remains unclear. There are no reports of male-to-male transmission in familial cases and cases of severely affected females have been reported. X-linked dominant, semi-dominant and recessive inheritance have been suggested and skewed X-inactivation has not been excluded.
Management and treatment
Management is supportive and should be multidisciplinary (involving a neurologist, orthopaedic surgeon and physical therapist).
The prognosis is generally severe: disease progression results in loss of ambulation, and death due to respiratory failure occurs even in patients with later-onset slowly progressive forms of the disease.