A Rare Case of Dysferlinopathy Causing Cardiomyopathy

Abstract

Introduction We report a case of a 30-year-old man who presented with advanced heart failure secondary to dilated cardiomyopathy. The patient was diagnosed with limb girdle muscular dystrophy type 2B (LGMD2B), a rare autosomal recessive disease. Cardiomyopathy is only rarely described in dysferlinopathies. Case This patient is a 30-year old African American male with medical history of left foot crush injury in 2016. The following year after injury he developed progressive exercise intolerance and palpitations. An electrocardiogram (ECG) showed sinus tachycardia. Echocardiogram revealed a severely dilated left ventricle, with increased wall thickness, apical trabeculations and ejection fraction (EF) of 20%. Right ventricle had normal size and function, and there was no significant valvular disease. His functional capacity and cardiac performance on imaging tests did not improve despite guideline directed medical therapy. He also had persistently elevated transaminases. Chronic liver disease workup was negative with liver biopsy showing mild sinusoidal dilatation without significant fibrosis. Persistently elevated transaminases in the absence of liver disease and significant systemic congestion prompted testing for muscle enzymes, which were severely elevated (CK-16,196; Aldolase 84.3 U/l). Neurologic examined revealed mild proximal muscle weakness. Further evaluation included electromyography (EMG), which was consistent with chronic myopathy. Genetic testing revealed a pathogenic splice site variant (c.2643+1GA), and two variants of uncertain significance (p.Asn367Lys, p.Arg553His) in the dysferlin gene. Muscle biopsy was performed which showed active myopathic features with myofiber necrosis and regeneration (Figure 1A, 1B). No chronic remodeling was present. Immunohistochemical staining showed loss of dysferlin expression (figure 1C; insert normal control). Expression of other sarcolemmal proteins like dystrophin was preserved (figure 1D). The biopsy findings support a diagnosis of a dysferlinopathy in the context of the described genetic variants and argue for the combination of the described variants to be disease causing. Conclusion LGMD2B is a rare limb girdle muscular dystrophy with very few previously reported cases of cardiac muscle involvement. Our case highlights the importance of a comprehensive diagnostic evaluation of idiopathic cardiomyopathy in young patients. Chronically elevated transaminases in young patients should prompt evaluation for myopathy, and genetic evaluation in the appropriate clinical context.