Pathogenesis, clinical features and diagnosis of sarcoglycanopathies

ABSTRACT

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.

KEYWORDS:

• Sarcoglycan
• limb girdle muscular dystrophy
• LGMD
• protein diagnosis
• genetic diagnosis
• treatment

Article highlights

• An accurate diagnosis also has a relevant importance at the psychological level to the patient and family. The gold standard for a precise diagnosis is the identification of causative gene mutations.

• Accurate molecular diagnosis of sarcoglycanopathy patients is crucial to offer precise genetic counselling and clinical care for these patients, as the frequency of severe complications in specific subgroups of patients makes this essential for effective management.

• The diagnostic process needs an integrated approach that starts clinically and ends with genetic testing.

• Muscle imaging, although still rarely explored in sarcoglycanopathy cases, might be a useful tool to evaluate disease progression and efficacy of clinical trials.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.