Pathogenesis, clinical features and diagnosis of sarcoglycanopathies

Introduction: By reviewing the literature from the last twenty years we present an accurate assessment of the state of the art in the pathogenesis and clinical presentations of sarcoglycanopathies, as well as the progress in diagnosis and treatment. Areas covered: Sarcoglycanopathies usually have a childhood onset but they can occur in adults with a limb girdle phenotype. Four main genes are expressed in the sarcoglycan complex. Cases with beta- or delta-sarcoglycan primary deficiency often present severe cardiac and respiratory complications. A defect of nitric oxide synthase might contribute to the pathogenesis of cardiac involvement and fatigue. Neuroimaging shows that muscle involvement affects mainly proximal muscle groups, followed by fibro-fatty replacement. Expert opinion: In cases of children with high creatine kinase levels and weakness or adults with limb girdle weakness, immunolabelling of muscle biopsy with anti-sarcoglycan antibodies may suggest the diagnosis, which should be confirmed by mutation analysis in the sarcoglycan genes. New genetic technologies, such as next generation sequencing, might be useful to obtain a molecular diagnosis, which is necessary for genetic counselling.