Pseudometabolic presentation of dystrophinopathy due to a missense mutation

Abstract

Exercise intolerance with myalgia, muscle stiffness, and recurrent rhabdomyolysis due to mutations in the DMD gene can mimic metabolic myopathies leading to delayed or inaccurate diagnoses. In this retrospective chart review, we report 3 unrelated boys with exertional myalgia, muscle stiffness, myoglobinuria, and normal neurological examination due to an identical point mutation in the DMD gene: a hemizygous T-to-C change in exon 15 (c.1724T>C) resulting in an amino acid substitution of leucine to proline at codon 575. Two of the 3 boys had normal dystrophin immunostaining and Western blot analysis in muscle. This missense mutation has been reported twice before, with at least 1 patient exhibiting rhabdomyolysis. Our report, however, is the first to describe in detail the clinical findings associated with this specific mutation. Further studies and clinical reports are needed to better understand the pathogenicity of the mutation.

FIGURE 1

Hematoxylin and eosin (H&E) staining of the muscle biopsy from patient 1 demonstrating fiber size variation, internal nuclei, and increased perimysial fibrosis. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 2

H&E staining of the muscle biopsy from patient 2 demonstrating fiber size variation, fiber necrosis, internal nuclei, and increased perimysial fibrosis. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]